ΔNp63α is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis
Open accessAbstract
SUMMARY The p53 homolog p63 is essential for development, yet its role in cancer is not clear. We discovered that p63 deficiency evokes the tumor suppressive mechanism of cellular senescence, causing a striking absence of stratified epithelia such as the skin. Here we identify the predominant p63 isoform, ΔNp63α, as a protein that bypasses oncogene induced senescence to drive tumorigenesis in vivo. Interestingly, bypass of senescence promotes stem-like proliferation and maintains survival of the keratin 15-positive stem cell population. Furthermore, we identify the chromatin remodeling protein Lsh as a new target of ΔNp63α that is an essential mediator of senescence bypass. These findings indicate that ΔNp63α is an oncogene that cooperates with Ras to promote tumor-initiating stem-like proliferation, and suggest that Lsh-mediated chromatin remodeling events are critical to this process.
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Specific TFs were essential, including TP63, FOSL1, and JUNB.
“Specific TFs were also essential, including TP63, the epidermal master regulator and cSCC oncogene (Keyes et al., 2011), as well as the AP1 family TFs, FOSL1 and JUNB.”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Keyes et al., 2011
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Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 1× · see citing works
“As shown previously, Ras induced features of senescence, including proliferation arrest, a characteristic morphology, and enhanced senescence-associated b-galactosidase (SA-b-gal) activity (Figure 1; Serrano et al., 1997).”
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649 · cited 1× · see citing works
“In contrast to the viable and fertile, yet tumor-prone, phenotype of p53-deficient mice (Donehower et al., 1992; Jacks et al., 1994), p63-deficient mice die postnatally from severe developmental anomalies, including a lack of skin and associated derivatives, an absence of glands such as prostate and breast, and trunca…”
p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
Yang, A., Schweitzer, R., Sun, D., Kaghad, M., Walker, N., Bronson, R. T., Tabin, C. J., Sharpe, A. H., Caput, D., Crum, C. P., et al. (1999) · Nature · doi:10.1038/19539 · Cited by 2,224 · see citing works
Crypt stem cells as the cells-of-origin of intestinal cancer
Barker, N., Ridgway, R. A., van Es, J. H., van de Wetering, M., Begthel, H., van den Born, M., Danenberg, E., Clarke, A. R., Sansom, O. J., & Clevers, H. C. (2008) · Nature · doi:10.1038/nature07602 · Cited by 2,159 · cited 1× · see citing works
“In some tumors, the cell of origin is suggested to be a normal somatic stem cell that has acquired mutations that allow it to transform (Barker et al., 2009).”
Yang, A., Kaghad, M., Wang, Y., Gillett, E. S., Fleming, M. D., Dötsch, V., Andrews, N. C., Caput, D., & McKeon, F. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80275-0 · Cited by 2,086 · see citing works
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051 · see citing works
Defining the Epithelial Stem Cell Niche in Skin
Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W. E., Rendl, M., & Fuchs, E. (2004) · Science · doi:10.1126/science.1092436 · Cited by 2,031 · cited 1× · see citing works
“Genes whose expression is elevated in the keratinocyte stem cell populations of mouse skin have been identified (Blanpain et al., 2004; Mignone et al., 2007; Tumbar et al., 2004).”
p63 is a p53 homologue required for limb and epidermal morphogenesis
Mills, A. A., Zheng, B., Wang, X., Vogel, H. S., Roop, D. R., & Bradley, A. (1999) · Nature · doi:10.1038/19531 · Cited by 1,974 · cited 1× · see citing works
“, 1994), p63-deficient mice die postnatally from severe developmental anomalies, including a lack of skin and associated derivatives, an absence of glands such as prostate and breast, and truncation of limbs (Mills et al., 1999; Yang et al., 1999).”
Self-citationEpigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?
Baylin, S. B., & Ohm, J. E. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1799 · Cited by 1,632 · see citing works
Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
Jamieson, C. H. M., Ailles, L. E., Dylla, S. J., Muijtjens, M., Jones, C., Zehnder, J. L., Gotlib, J., Li, K., Manz, M. G., Keating, A., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040258 · Cited by 1,485 · see citing works
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482 · cited 1× · see citing works
“Topical treatment of mouse skin with DMBA induces Ras mutations, which facilitate development of premalignant papillomas with markers and features of OIS; inactivation of mediators of OIS facilitates senescence bypass and converts preneoplastic lesions tomalignant SCC (Collado et al., 2005).”
Blanpain, C., Lowry, W. E., Geoghegan, A., Polak, L., & Fuchs, E. (2004) · Cell · doi:10.1016/j.cell.2004.08.012 · Cited by 1,428 · see citing works
p63 identifies keratinocyte stem cells
Pellegrini, G., Dellambra, E., Golisano, O., Martinelli, E., Fantozzi, I., Bondanza, S., Ponzin, D., McKeon, F., & Luca, M. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061032098 · Cited by 1,359 · cited 1× · see citing works
“There is accumulating evidence that p63, and in particular the DNp63a isoform, maintains the proliferative capacity of epithelial stem cells of the skin, thymus, prostate, breast, and eye (Pellegrini et al., 2001; Senoo et al., 2007; Xin et al., 2007).”
Capturing and profiling adult hair follicle stem cells
Morris, R. J., Liu, Y., Marles, L., Yang, Z., Trempus, C., Li, S., Lin, J. S., Sawicki, J. A., & Cotsarelis, G. (2004) · Nature Biotechnology · doi:10.1038/nbt950 · Cited by 1,283 · cited 2× · see citing works
“C which the K15 promoter drives GFP expression in stem cells of the hair follicle bulge that can give rise to all epidermal cell types (Morris et al., 2004).”
p63 Is Essential for the Proliferative Potential of Stem Cells in Stratified Epithelia
Senoo, M., Pinto, F., Crum, C. P., & McKeon, F. (2007) · Cell · doi:10.1016/j.cell.2007.02.045 · Cited by 881 · cited 3× · see citing works
“There is accumulating evidence that p63, and in particular the DNp63a isoform, maintains the proliferative capacity of epithelial stem cells of the skin, thymus, prostate, breast, and eye (Pellegrini et al., 2001; Senoo et al., 2007; Xin et al., 2007).”
A Mutant-p53/Smad Complex Opposes p63 to Empower TGFβ-Induced Metastasis
Adorno, M., Cordenonsi, M., Montagner, M., Dupont, S., Wong, C., Hann, B. C., Solari, A., Bobisse, S., Rondina, M. B., Guzzardo, V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.039 · Cited by 783 · see citing works
Heterozygous Germline Mutations in the p53 Homolog p63 Are the Cause of EEC Syndrome
Celli, J., Duijf, P. H. G., Hamel, B. C. J., Bamshad, M. J., Kramer, B., Smits, A., Newbury-Ecob, R. A., Hennekam, R. C. M., Buggenhout, G. V., van Haeringen, A., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81646-3 · Cited by 707 · cited 1× · see citing works
“The R279H mutation within the DNA binding domain of p63 causes EEC syndrome in humans and corresponds to one of the most prevalent p53 point mutations found in human cancer (Celli et al., 1999).”
Dai, C., Celestino, J., Okada, Y., Louis, D. N., Fuller, G. N., & Holland, E. C. (2001) · Genes & Development · doi:10.1101/gad.903001 · Cited by 707 · cited 1× · see citing works
“In contrast with tumors such as pancreatic intraepithelial neoplasia and malignant astrocytomas, in which Nestin-positive stem/progenitor cells are the source of malignancy after oncogene activation or tumor-suppressor loss (Alcantara Llaguno et al., 2009; Carrière et al., 2007; Dai et al., 2001), our data suggest tha…”
Neural stem and progenitor cells in nestin‐GFP transgenic mice
Mignone, J., Kukekov, V. G., Chiang, A., Steindler, D. A., & Enikolopov, G. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.10964 · Cited by 705 · see citing works
Self-citationAlcantara Llaguno, S., Chen, J., Kwon, C.-H., Jackson, E. L., Li, Y., Burns, D. K., Alvarez-Buylla, A., & Parada, L. F. (2009) · Cancer Cell · doi:10.1016/j.ccr.2008.12.006 · Cited by 694 · see citing works
Isolation and Characterization of Multipotent Skin‐Derived Precursors from Human Skin
Toma, J. G., McKenzie, I. A., Bägli, D., & Miller, F. D. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0134 · Cited by 678 · cited 1× · see citing works
“, 2009)—a progenitor population that gives rise to neuronal and mesenchymal cell types, but not to epithelial cell types such as keratinocytes (Fernandes et al., 2008; Toma et al., 2005).”
Probing tumor phenotypes using stable and regulated synthetic microRNA precursors
Dickins, R., Hemann, M., Zilfou, J. T., Simpson, D. R., Ibarra, I., Hannon, G., & Lowe, S. (2005) · Nature Genetics · doi:10.1038/ng1651 · Cited by 561 · cited 1× · see citing works
“html) website, cloned into LMP vectors (Dickins et al., 2005), evaluated for efficiency in mouse embryonic fibroblasts (mefs), and assessed by western blotting 2 days after drug selection.”
p63 expression profiles in human normal and tumor tissues.
Como, C. J. D., Urist, M. J., Babayan, I., Drobnjak, M., Hedvat, C. V., Teruya‐Feldstein, J., Kamal, P., Hoos, A., & Cordon‐Cardo, C. (2002) · PubMed · Cited by 511 · see citing works
Flores, E. R., Sengupta, S., Miller, J. B., Newman, J. J., Bronson, R. T., Crowley, D. G., Yang, A., McKeon, F., & Jacks, T. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.02.019 · Cited by 499 · cited 1× · see citing works
“The tumorigenic potential of p63-deficient mice has surprisingly not helped to clarify the role of p63 in cancer, because different groups have reported disparate results (Flores et al., 2005; Keyes et al., 2006).”
AIS is an oncogene amplified in squamous cell carcinoma
Hibi, K., Trink, B., Patturajan, M., Westra, W. H., Caballero, O. L., Hill, D. E., Ratovitski, E. A., Jen, J., & Sidransky, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5462 · Cited by 464 · cited 3× · see citing works
“In further contrast to p53, the predominant p63 isoform detectable in proliferating epithelia, DNp63a, is frequently overexpressed in a variety of human tumors, particularly SCC of the skin, head and neck, and lung (Hibi et al., 2000; Tonon et al., 2005), although an oncogenic role for DNp63a had not”
Influentialp63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis
Rocco, J. W., Leong, C., Kuperwasser, N., DeYoung, M. P., & Ellisen, L. W. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.013 · Cited by 435 · cited 1× · see citing works
“shown to rely on enhanced DNp63a expression (Rocco et al., 2006).”
Isolation and functional characterization of murine prostate stem cells
Lawson, D. A., Xin, L., Lukacs, R. U., Cheng, D., & Witte, O. N. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609684104 · Cited by 399 · see citing works
Lsh, a member of the SNF2 family, is required for genome-wide methylationPreprint
Dennis, K., Fan, T., Geiman, T. M., Yan, Q., & Muegge, K. (2001) · Genes & Development · doi:10.1101/gad.929101 · Cited by 381 · see citing works
Assou, S., Carrour, T. L., Tondeur, S., Ström, S., Gabelle, A., Marty, S., Nadal, L., Pantesco, V., Reme, T. X., Hugnot, J., et al. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0352 · Cited by 343 · cited 1× · see citing works
“Our identification of Lsh, a chromatin-remodeling protein robustly expressed in human embryonic stem cells (Assou et al., 2007), as a DNp63a target suggests that p63 plays a role in epigenetic regulation of stemness.”
Missero, C., Cunto, F. D., Kiyokawa, H., Koff, A., & Dotto, G. P. (1996) · Genes & Development · doi:10.1101/gad.10.23.3065 · Cited by 312 · see citing works
p63 deficiency activates a program of cellular senescence and leads to accelerated agingPreprint
Keyes, W. M., Wu, Y., Vogel, H. S., Guo, X., Lowe, S. W., & Mills, A. A. (2005) · Genes & Development · doi:10.1101/gad.342305 · Cited by 296 · cited 10× · see citing works
“To assess whether DNp63a is required for Lsh expression, we ablated p63 in primary keratinocytes obtained from the p63 conditional mouse model that we described previously (Keyes et al., 2005; Mills et al., 2002).”
InfluentialSelf-citationCao, L., Li, W., Kim, S., Brodie, S. G., & Deng, C.-X. (2003) · Genes & Development · doi:10.1101/gad.1050003 · Cited by 293 · cited 1× · see citing works
“, 2007), and Brca1 (Cao et al., 2003).”
Self-citationYang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G. M., Gingeras, T., & Struhl, K. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.10.018 · Cited by 277 · see citing works
TAp63 induces senescence and suppresses tumorigenesis in vivo
Guo, X., Keyes, W. M., Papazoglu, C., Zuber, J. A., Li, W., Lowe, S. W., Vogel, H. S., & Mills, A. A. (2009) · Nature Cell Biology · doi:10.1038/ncb1988 · Cited by 252 · cited 2× · see citing works
“, 2005) and more recently found that TAp63 isoforms are essential inducers of OIS that halt both the initiation and progression of Ras-driven p53-deficient tumors in vivo (Guo et al., 2009).”
Self-citationTAp63 Prevents Premature Aging by Promoting Adult Stem Cell Maintenance
Su, X., Paris, M., Gi, Y. J., Tsai, K. Y., Cho, M. S., Lin, Y.-L., Biernaskie, J., Sinha, S., Prives, C. L., Pevny, L., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.04.003 · Cited by 251 · cited 1× · see citing works
“A recent report suggests that the TAp63 isoforms also function to regulate senescence within a different stem cell niche, inhibiting cellular senescence in skin-derived progenitor cells (SKPs) (Su et al., 2009)—a progenitor population that gives rise to neuronal and mesenchymal cell types, but not to epithelial cell t…”
Aranda, V., Haire, T., Nolan, M. E., Calarco, J. P., Rosenberg, A. Z., Fawcett, J. P., Pawson, T. J., & Muthuswamy, S. K. (2006) · Nature Cell Biology · doi:10.1038/ncb1485 · Cited by 243 · cited 2× · see citing works
“For immunofluorescence, cultures were fixed and stained as described (Aranda et al., 2006), with antiK14 polyclonal antibody AF64 (Covance Research Products Inc.”
Self-citationSelf-Renewal and Multilineage Differentiation In Vitro from Murine Prostate Stem Cells
Xin, L., Lukacs, R. U., Lawson, D. A., Cheng, D., & Witte, O. N. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0355 · Cited by 199 · see citing works
Gemenetzidis, E., Bose, A., Riaz, A., Chaplin, T., Young, B. D., Ali, M., Sugden, D., Thurlow, J. K., Cheong, S., Teo, S., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004849 · Cited by 189 · cited 1× · see citing works
“Although the mechanism by which DNp63a-driven Lsh expression facilitates senescence bypass and tumor development remain to be elucidated, a recent report that Lsh is overexpressed in human HNSCC (Gemenetzidis et al., 2009) supports our finding that DNp63a promotes tumorigenesis via induction of Lsh-mediated bypass of…”
Sun, L.-Q., Lee, D. W., Zhang, Q., Xiao, W., Raabe, E. H., Meeker, A. K., Miao, D., Huso, D. L., & Arceci, R. J. (2004) · Genes & Development · doi:10.1101/gad.1176104 · Cited by 182 · cited 6× · see citing works
“Interestingly, mouse models deficient for three of these candidates have phenotypes of cellular senescence or organismal aging: Lsh (Sun et al., 2004), Exo1 (Schaetzlein et al.”
InfluentialThe p63 gene in EEC and other syndromes
Brunner, H. G., Hamel, B. C. J., & van Bokhoven, H. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.6.377 · Cited by 179 · cited 1× · see citing works
“Unlike p53, point mutations in p63 are rarely associated with cancer, but cause a spectrum of developmental birth defects (Brunner et al., 2002).”
Narita, M., & Lowe, S. W. (2005) · Nature Medicine · doi:10.1038/nm0905-920 · Cited by 150 · cited 1× · see citing works
“OIS is a tumor-suppressive mechanism that curtails aberrant proliferation of cells responding to DNA damage or oncogenic signaling, a program mediated predominantly by tumor suppressors such as p53, p16, and Rb (Narita and Lowe, 2005).”
Schaetzlein, S., Nalapareddy, K., Ju, Z., Lechel, A., Stępczyńska, A., Lilli, D. R., Clark, A. B., Rudolph, C., Kühnel, F., Wei, K., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.029 · Cited by 144 · cited 1× · see citing works
“, 2004), Exo1 (Schaetzlein et al., 2007), and Brca1 (Cao et al.”
Lsh, an epigenetic guardian of repetitive elements
Huang, J. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh821 · Cited by 139 · cited 1× · see citing works
“In particular, Lsh is required for methylation-induced silencing of repeat elements and transposons in the pericentromeric regions (Huang et al., 2004; Sun et al., 2004) and also causes transcriptional silencing of individual loci including Cdkn1c/p57 (Sun et al.”
The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia
Carrière, C., Seeley, E. S., Goetze, T., Longnecker, D. S., & Korc, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701117104 · Cited by 138 · cited 1× · see citing works
“In contrast with tumors such as pancreatic intraepithelial neoplasia and malignant astrocytomas, in which Nestin-positive stem/progenitor cells are the source of malignancy after oncogene activation or tumor-suppressor loss (Alcantara Llaguno et al., 2009; Carrière et al., 2007; Dai et al., 2001), our data suggest tha…”
LSH Cooperates with DNA Methyltransferases To Repress Transcription
Myant, K., & Stancheva, I. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01073-07 · Cited by 137 · cited 1× · see citing works
“Lsh functions by recruiting DNAmethyltransferases (Myant and Stancheva, 2008) or through direct interaction withmembers of the Polycomb repressive complex 1 (Xi et al.”
Fernandes, K. J. L., Toma, J. G., & Miller, F. D. (2007) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.2020 · Cited by 129 · cited 1× · see citing works
“, 2009)—a progenitor population that gives rise to neuronal and mesenchymal cell types, but not to epithelial cell types such as keratinocytes (Fernandes et al., 2008; Toma et al., 2005).”
Signal Transduction Pathways Controlling the Switch Between Keratinocyte Growth and Differentiation
Dotto, G. P. (1999) · Critical Reviews in Oral Biology & Medicine · doi:10.1177/10454411990100040201 · Cited by 101 · cited 1× · see citing works
“We askedwhether RDN cells have this capacity by taking advantage of the ability of primary keratinocytes to terminally differentiate and to withdraw from the cell cycle in the presence of elevated calcium (Dotto, 1999).”
Lsh, a SNF2 family member, is required for normal murine development
Geiman, T. M., Tessarollo, L., Anver, M. R., Kopp, J. B., Ward, J. M., & Muegge, K. (2001) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(01)00129-5 · Cited by 91 · cited 2× · see citing works
“Lsh plays a key role in senescence and aging, with Lsh-deficient mice exhibiting either postnatal lethality (Geiman et al., 2001) or aberrant aging and enhanced cellular senescence (Sun et al.”
p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors
Keyes, W. M., Vogel, H. S., Koster, M. I., Guo, X., Qi, Y., Petherbridge, K. M., Roop, D. R., Bradley, A., & Mills, A. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602477103 · Cited by 88 · see citing works
Self-citationNeural Potential of a Stem Cell Population in the Hair Follicle
Mignone, J., Roig-López, J. L., Fedtsova, N. G., Schones, D. E., Manganas, L. N., Maletić‐Savatić, M., Keyes, W. M., Mills, A. A., Gleiberman, A. S., Zhang, M. Q., et al. (2007) · Cell Cycle · doi:10.4161/cc.6.17.4593 · Cited by 80 · cited 2× · see citing works
“Genes whose expression is elevated in the keratinocyte stem cell populations of mouse skin have been identified (Blanpain et al., 2004; Mignone et al., 2007; Tumbar et al., 2004).”
Self-citationLsh controls Hox gene silencing during development
Xi, S., Zhu, H., Xu, H., Schmidtmann, A., Geiman, T. M., & Muegge, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703669104 · Cited by 71 · cited 2× · see citing works
“Lsh functions by recruiting DNAmethyltransferases (Myant and Stancheva, 2008) or through direct interaction withmembers of the Polycomb repressive complex 1 (Xi et al., 2007).”
Lsh, a guardian of heterochromatin at repeat elements
Muegge, K. (2005) · Biochemistry and Cell Biology · doi:10.1139/o05-119 · Cited by 63 · cited 2× · see citing works
“Lsh regulates DNA methylation and transcriptional silencing (Muegge, 2005), as indicated by the fact that its deficiency causes DNA hypomethylation, altered histone modification, and alterations in heterochromatin (Dennis et al.”
Ortt, K., & Sinha, S. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.07.004 · Cited by 62 · cited 1× · see citing works
“p63 consensus-binding sitesWDDCNDGHHD {1-25}WDDCNDGHHDwere identified with modifications of previously published motifs (Ortt and Sinha, 2006; Yang et al., 2006).”
Conditional inactivation of p63 by Cre‐mediated excision
Mills, A. A., Qi, Y., & Bradley, A. (2002) · genesis · doi:10.1002/gene.10067 · Cited by 46 · cited 2× · see citing works
“To assess whether DNp63a is required for Lsh expression, we ablated p63 in primary keratinocytes obtained from the p63 conditional mouse model that we described previously (Keyes et al., 2005; Mills et al., 2002).”
Self-citationCommon and Contrasting Genomic Profiles among the Major Human Lung Cancer SubtypesPreprint
Tonon, G., Brennan, C. W., Protopopov, A. I., Maulik, G., Feng, B., ZHANG, Y., Khatry, D., You, M. J., Aguirre, A. J., Martin, E. S., et al. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.021 · Cited by 19 · see citing works
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Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
Ji, A. L., Rubin, A. J., Thrane, K., Jiang, S., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A., Bergenstråhle, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.039 · Cited by 1,117 · see citing works
“Specific TFs were also essential, including TP63, the epidermal master regulator and cSCC oncogene (Keyes et al., 2011), as well as the AP1 family TFs, FOSL1 and JUNB.”
BackgroundSenescence and aging: the critical roles of p53
Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798 · see citing works
Wang, M., Mao, C., Ouyang, L., Liu, Y., Lai, W., Liu, N., Shi, Y., Chen, L., Xiao, D., Yu, F., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0304-y · Cited by 530 · see citing works
Nowell, C. S., & Radtke, F. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.145 · Cited by 370 · see citing works
Andricovich, J., Perkail, S., Kai, Y., Casasanta, N., Peng, W., & Tzatsos, A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.003 · Cited by 320 · see citing works
“A molecular hallmark of the “C2-squamous-like” subtype is strong upregulation of the ΔNp63 isoform which has been linked to squamous identity (Hoadley et al., 2014; Keyes et al., 2011).”
BackgroundChilosi, M., Carloni, A., Rossi, A., & Poletti, V. E. (2013) · Translational research · doi:10.1016/j.trsl.2013.06.004 · Cited by 314 · see citing works
Jiang, Y., Mao, C., Yang, R., Yan, B., Shi, Y., Liu, X., Lai, W., Liu, Y., Wang, X., Xiao, D., et al. (2017) · Theranostics · doi:10.7150/thno.19988 · Cited by 293 · see citing works
TP63-mediated enhancer reprogramming drives the squamous subtype of pancreatic ductal adenocarcinoma
Somerville, T. D. D., Xu, Y., Miyabayashi, K., Tiriac, H., Cleary, C. R., Maia-Silva, D., Milazzo, J. P., Tuveson, D. A., & Vakoc, C. R. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.051 · Cited by 225 · see citing works
“Considering the known link between ∆Np63 and squamous cell carcinoma (Keyes et al., 2011), we investigated whether manipulating this TF would allow us to understand the importance of squamous lineage characteristics in PDA.”
BackgroundCo-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression
Jiang, Y. Y., Jiang, Y.-Y., Xie, J., Mayakonda, A., Hazawa, M., Chen, L., Xiao, J.-F., Li, C., Huang, M., Ding, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06081-9 · Cited by 227 · see citing works
p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53
Melino, G. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.81 · Cited by 226 · see citing works
Epigenetic control of adult stem cell function
Avgustinova, A., & Benitah, S. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.76 · Cited by 216 · see citing works
Single cell transcriptomics of human epidermis identifies basal stem cell transition states
Wang, S., Drummond, M. L., Guerrero-Juarez, C. F., Tarapore, E., MacLean, A. L., Stabell, A. R., Wu, S. C., Gutierrez, G., That, B. T., Benavente, C. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18075-7 · Cited by 218 · see citing works
Biological functions of p53 isoforms through evolution: lessons from animal and cellular models
Marcel, V., Dichtel-Danjoy, M.-L., Sagne, C., Hafsi, H., Ma, D., Ortiz‐Cuaran, S., Olivier, M., Hall, J. A., Mollereau, B., Hainaut, P. L., et al. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.120 · Cited by 210 · see citing works
Chakrabarti, R., Wei, Y., Hwang, J., Hang, X., Blanco, M. A., Choudhury, A., Tiede, B., Romano, R. A., DeCoste, C. J., Mercatali, L., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3040 · Cited by 207 · see citing works
Saladi, S. V., Ross, K. N., Karaayvaz, M., Tata, P. R., Mou, H., Rajagopal, J., Ramaswamy, S., & Ellisen, L. W. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.12.001 · Cited by 195 · see citing works
“In addition, forced expression of DNp63a, the major p63 isoform present in tumors and normal epithelia, is sufficient to bypass senescence and drive stemlike proliferation and tumorigenesis (Ha et al., 2011; Keyes et al., 2011).”
BackgroundSOX2 and p63 colocalize at genetic loci in squamous cell carcinomas
Watanabe, H., Ma, Q., Peng, S., Adelmant, G., Swain, D., Song, W., Fox, C., Francis, J. M., Pedamallu, C. S., DeLuca, D. S., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71545 · Cited by 185 · see citing works
“org 7 SCCs from keratinocytes by promoting progenitor cell expansion (45).”
Master regulatory role of p63 in epidermal development and disease
Soares, E., & Zhou, H. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2701-z · Cited by 183 · see citing works
“Chromatin remodelers that are direct p63 targets also include LSH, which regulates DNA methylation and transcriptional silencing [60].”
BackgroundKumar, S., Wilkes, D. W., Samuel, N., Blanco, M. A., Nayak, A., Alicea-Torres, K. M., Gluck, C. B., Sinha, S., Gabrilovich, D. I., & Chakrabarti, R. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99673 · Cited by 174 · see citing works
Age-associated inflammation inhibits epidermal stem cell functionPreprint
Doles, J. D., Storer, M. A., Cozzuto, L., Roma, G., & Keyes, W. M. (2012) · Genes & Development · doi:10.1101/gad.192294.112 · Cited by 167 · see citing works
“…of tumor initiation and that this Krt-15 stem cell population was recently identified as a target cell of origin in squamous cell carcinoma (Keyes et al. 2011; Lapouge et al. 2011; White et al. 2011), the expansion of this population during aging could significantly increase the chance of…”
BackgroundSelf-citationSenescence Regulation by the p53 Protein Family
Qian, Y., & Chen, X. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-239-1_3 · Cited by 170 · see citing works
Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas
Botti, E., Spallone, G., Moretti, F., Marinari, B., Pinetti, V., Galanti, S., Meo, P. D. D., Nicola, F. D., Ganci, F., Castrignanò, T., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110931108 · Cited by 169 · see citing works
“S1A) and the recent discovery that ΔNp63 plays a critical role in inducing bypass of OIS (26) prompted us to analyze the role of IRF6 in regulating this early event.”
BackgroundInfluentialTran, M., Choi, W., Wszolek, M. F., Navai, N., Lee, I.-L. C., Nitti, G., Wen, S., Flores, E. R., Siefker-Radtke, A. O., Czerniak, B. A., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.408104 · Cited by 145 · see citing works
Epigenetic Regulation of Skin Cells in Natural Aging and Premature Aging Diseases
Orioli, D., & Dellambra, E. (2018) · Cells · doi:10.3390/cells7120268 · Cited by 144 · see citing works
“Furthermore, Lsh is a direct target of both p63 [147] and DNMT1 [160] that may cooperate to repress p16INK4a expression and maintain a proliferative state in epidermal progenitors.”
Backgroundp63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis
Su, X., Chakravarti, D., & Flores, E. R. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3446 · Cited by 139 · see citing works
FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma
Ramsey, M. R., Wilson, C., Ory, B., Rothenberg, S. M., Faquin, W. C., Mills, A. A., & Ellisen, L. W. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68899 · Cited by 112 · see citing works
Self-citationp53/p63/p73 in the Epidermis in Health and DiseasePreprint
Botchkarev, V. A., & Flores, E. R. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a015248 · Cited by 111 · see citing works
“In turn, Lsh regulates chromatin remodeling and mediates DNp63-dependent proliferation and survival of Keratin 15-positive stem cells in the skin (Keyes et al. 2011).”
BackgroundRole of p63 in Development, Tumorigenesis and Cancer Progression
Bergholz, J. S., & Xiao, Z. J. (2012) · Cancer Microenvironment · doi:10.1007/s12307-012-0116-9 · Cited by 111 · see citing works
“It has been shown that concomitant ΔNp63α and Ras expression cooperate to induce tumor formation in mouse xenografts, while either Ras or ΔNp63α over-expression alone is not enough for supporting tumor growth, thus indicating thatΔNp63α may also act as an oncogene by potentiating the oncogenic features of Ras [92].”
BackgroundDatson, N. A., van den Oever, J. M. E., Korobko, O. B., Magariños, A. M., de Kloet, E. R., & McEwen, B. S. (2013) · Endocrinology · doi:10.1210/en.2012-2233 · Cited by 105 · see citing works
He, X., Yan, B., Liu, S., Jia, J., Lai, W., Xing, X., Tang, C., Luo, D., Tan, T., Jiang, Y., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0268 · Cited by 102 · see citing works
Cutaneous Notch Signaling in Health and DiseasePreprint
Nowell, C., & Radtke, F. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a017772 · Cited by 100 · see citing works
“As described above, Notch1 inhibits DNp63a expression, which promotes proliferation of epithelial stem cells and can exert oncogenic effects in the skin (Keyes et al. 2011).”
BackgroundMolecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis
Moses, M. A., George, A. L., Sakakibara, N., Mahmood, K., Ponnamperuma, R. M., King, K. E., & Weinberg, W. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143590 · Cited by 99 · see citing works
p53 Family: Role of Protein Isoforms in Human Cancer
Wei, J., Zaika, E. I., & Zaika, A. I. (2012) · Journal of Nucleic Acids · doi:10.1155/2012/687359 · Cited by 97 · see citing works
Np63 Regulates Stem Cell Dynamics in the Mammalian Olfactory Epithelium
Packard, A., Schnittke, N., Romano, R.-A., Sinha, S., & Schwob, J. E. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0681-11.2011 · Cited by 95 · see citing works
“…which mediate adhesion to the basal lamina, such as integrins (Carroll et al., 2006); components of signaling pathways including the Notch and Wnt pathways (Laurikkala et al., 2006; Romano et al., 2010; Yalcin-Ozuysal et al., 2010), and chromatin remodeling components (Keyes et al., 2011).”
Backgroundp63-related signaling at a glance
Fisher, M. L., Balinth, S., & Mills, A. A. (2020) · Journal of Cell Science · doi:10.1242/jcs.228015 · Cited by 92 · see citing works
“Another chromatin-modifying protein that is regulated by p63 is lymphoid-specific helicase (LSH; also known as HELLS) (Keyes et al., 2011), which is implicated in embryonic development and cellular senescence (Muegge, 2005).”
BackgroundSelf-citationp63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas
Hsieh, M.-H., Choe, J. H., Gadhvi, J. G., Kim, Y. J., Arguez, M. A., Palmer, M., Gerold, H., Nowak, C. M., Do, H., Mazambani, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.027 · Cited by 92 · see citing works
“Amplified ΔNp63 may cooperate with various oncogenic events, including activation of oncogenic Ras and β-catenin as well as repression of tumor suppressors p53 and p73, to endow an increased proliferative effect (Hibi et al., 2000; Keyes et al., 2011; Patturajan et al., 2002; Rocco et al., 2006; Yang et al., 1998).”
BackgroundYi, M., Tan, Y.-X., Wang, L., Cai, J., Li, X.-L., Zeng, Z.-Y., Xiong, W., Li, G.-Y., Li, X.-Y., Tan, P., et al. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03539-2 · Cited by 77 · see citing works
Danilov, A. V., Neupane, D., Nagaraja, A. S., Feofanova, E. V., Humphries, L. A., DiRenzo, J., & Korc, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026815 · Cited by 85 · see citing works
“Recent studies have indicated that DNp63a is necessary and sufficient to by-pass oncogene-induced senescence suggesting that it plays a critical role in the very early steps of cancer initiation [38].”
BackgroundHazawa, M., Lin, D., Kobayashi, A., Jiang, Y., Xu, L., Dewi, F. R. P., Mohamed, M. S., Hartono, H., Nakada, M., Meguro‐Horike, M., et al. (2017) · EMBO Reports · doi:10.15252/embr.201744523 · Cited by 85 · see citing works
p63: a crucial player in epithelial stemness regulation
Li, Y., Giovannini, S., Wang, T., Fang, J., Li, P., Shao, C., Wang, Y., Agostini, M., Bove, P., Mauriello, A., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02859-4 · Cited by 83 · see citing works
Teh, M., Gemenetzidis, E., Patel, D., Tariq, R., Nadir, A., Bahta, A. W., Waseem, A., & Hutchison, I. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034329 · Cited by 83 · see citing works
“Furthermore, our previous finding that FOXM1 expression co-expressed with an epithelial stem cell marker DNp63a in the proliferating stem/progenitor oral keratinocyte subpopulation [10], and that DNp63a has been shown to target HELLS to induce squamous cell carcinoma formation in mice [37], together suggest a possible…”
Myoepithelial Cell Differentiation Markers in Ductal Carcinoma in Situ Progression
Russell, T. D., Jindal, S., Agunbiade, S., Gao, D., Troxell, M. L., Borges, V. F., & Schedin, P. S. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.07.004 · Cited by 80 · see citing works
Wang, G. X., Tu, H.-C., Dong, Y., Skanderup, A. J., Wang, Y., Takeda, S., Ganesan, Y. T., Han, S. I., Liu, H., Hsieh, J. J.-D., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.030 · Cited by 78 · see citing works
Chemosensitivity is controlled by p63 modification with ubiquitin-like protein ISG15
Jeon, Y. J., Jo, M. G., Yoo, H. M., Hong, S.-H., Park, J.-M., Ka, S. H., Oh, K. H., Seol, J. H., Jung, Y., & Chung, C. H. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61762 · Cited by 76 · see citing works
Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma
Kumar, D., Gorain, M., Kundu, G., & Kundu, G. C. (2017) · Molecular Cancer · doi:10.1186/s12943-016-0578-3 · Cited by 78 · see citing works
“Interestingly, the isoform of p63, ΔNp63α bypasses the senescence to promote stem-like cell proliferation and tumorigenesis in skin cancer under in vivo condition [112].”
BackgroundA double dealing tale of p63: an oncogene or a tumor suppressor
Chen, Y., Peng, Y., Fan, S., Li, Y., Xiao, Z. J., & Li, C. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2666-y · Cited by 74 · see citing works
Balboni, A., Hutchinson, J. A., DeCastro, A., Cherukuri, P., Liby, K. T., Sporn, M. B., Schwartz, G. N., Wells, W. A., Sempere, L. F., Yu, P. B., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2862 · Cited by 70 · see citing works
The Role of p16INK4a Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer
D’Arcangelo, D., Tinaburri, L., & Dellambra, E. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071591 · Cited by 71 · see citing works
“Moreover, the chromatin remodeler LSH is a direct target of both p63 [101] and DNMT1 in primary keratinocytes.”
BackgroundMardaryev, A. N., Liu, B., Rapisarda, V., Poterlowicz, K., Malashchuk, I., Rudolf, J., Sharov, A. A., Jahoda, C. A. B., Fessing, M. Y., Benitah, S. A., et al. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201506065 · Cited by 66 · see citing works
“Increased evidence demonstrates that p63 regulates several components of the epigenetic machinery (Brg1, Lsh, and Satb1) to regulate chromatin remodeling and establish the epidermal differentiation program (Fessing et al., 2011; Keyes et al., 2011; Mardaryev et al., 2014).”
BackgroundTranscription Factor TCF4 Maintains the Properties of Human Corneal Epithelial Stem Cells
Lu, R., Qu, Y., Ge, J., Zhang, L., Su, Z., Pflugfelder, S. C., & Li, D. (2012) · Stem Cells · doi:10.1002/stem.1032 · Cited by 64 · see citing works
Oh, J.-E., Kim, R. H., Shin, K.-H., Park, N., & Kang, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.244939 · Cited by 62 · see citing works
Xiao, D., Huang, J. X., Pan, Y., Li, H. R., Fu, C., Mao, C., Cheng, Y., Shi, Y., Chen, L., Jiang, Y., et al. (2016) · Theranostics · doi:10.7150/thno.17032 · Cited by 62 · see citing works
Kollárovič, G., Topping, C. E., Shaw, E. P., & Chambers, A. L. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1146 · Cited by 62 · see citing works
USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma
Prieto‐Garcia, C., Tomašković, I., Shah, V. J., Đikić, I., & Diefenbacher, M. E. (2021) · Cells · doi:10.3390/cells10102652 · Cited by 61 · see citing works
“Furthermore, the oncogenic potential of ∆Np63α collaborates with the RAS pathway to induce tumorigenesis [89].”
BackgroundCapturing epidermal stemness for regenerative medicine
Barrandon, Y., Grasset, N., Zaffalon, A., Gorostidi, F., Claudinot, S., Droz-Georget, S. L., Nanba, D., & Rochat, A. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.09.011 · Cited by 60 · see citing works
“[102] Keyes WM, Pecoraro M, Aranda V, Vernersson-Lindahl E, Li W, Vogel H, et al.”
BackgroundAlterations of p63 and p73 in Human Cancers
Inoue, K., & Fry, E. A. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-017-9211-0_2 · Cited by 58 · see citing works
“[ 58 ] observed that ΔNp63 α overexpression in mouse embryonic fi broblasts (MEFs) bypassed Ras-mediated senescence and drove tumorigenesis in vivo .”
BackgroundHuman epidermal stem cells: Role in adverse skin reactions and carcinogenesis from radiation
Martin, M. T., Vulin, A., & Hendry, J. H. (2016) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2016.08.004 · Cited by 60 · see citing works
deltaNp63 Has a Role in Maintaining Epithelial Integrity in Airway Epithelium
Arason, A. J., Jónsdóttir, H. R., Halldórsson, S., Benediktsdóttir, B. E., Bergþorsson, J. Þ., Ingþórsson, S., Baldursson, Ó., Sinha, S., Guðjónsson, Þ., & Magnússon, M. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088683 · Cited by 58 · see citing works
Wang, R., Shi, Y., Chen, L., Jiang, Y., Mao, C., Yan, B., Liu, S., Shan, B., Tao, Y., & Wang, X. (2015) · Scientific Reports · doi:10.1038/srep17826 · Cited by 58 · see citing works
Novel approaches for managing aged skin and nonmelanoma skin cancer
Todorova, K. A., & Mandinova, A. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.004 · Cited by 59 · see citing works
ΔNp63α regulates Erk signaling via MKP3 to inhibit cancer metastasis
Bergholz, J. S., Zhang, Y., Wu, J., Le, M., Walsh, E. M., Rai, A., Sherman, M. Y., & Xiao, Z.-X. (2012) · Oncogene · doi:10.1038/onc.2012.564 · Cited by 57 · see citing works
“In line with these observations, ΔNp63α cooperates with Ras to promote skin stem cell proliferation and tumorigenesis (22).”
ΔNp63 Promotes Pediatric Neuroblastoma and Osteosarcoma by Regulating Tumor Angiogenesis
Bid, H. K., Roberts, R. D., Cam, M., Audino, A. N., Kurmasheva, R. T., Lin, J., Houghton, P. J., & Çam, H. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0894 · Cited by 57 · see citing works
Jia, J., Shi, Y., Chen, L., Lai, W., Yan, B., Jiang, Y., Xiao, D., Xi, S., Cao, Y., Liu, S., et al. (2017) · Theranostics · doi:10.7150/thno.21389 · Cited by 56 · see citing works
Sharma, M., Fonseca, F. P., Hunter, K. D., & Radhakrishnan, R. A. (2020) · International Journal of Oral Science · doi:10.1038/s41368-020-00090-5 · Cited by 55 · see citing works
Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer
Mulero, M. C., Ferrés-Marcó, D., Islam, A. B. M. M. K., Margalef, P., Pecoraro, M., Toll, A., Drechsel, N. J. D., Charneco, C., Davis, S. M., Bellora, N., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.003 · Cited by 55 · see citing works
Self-citationYang, R., Liu, N., Chen, L., Jiang, Y., Shi, Y., Mao, C., Liu, Y., Wang, M., Lai, W., Tang, H., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0909-0 · Cited by 54 · see citing works
ΔNp63α activates CD82 metastasis suppressor to inhibit cancer cell invasion
Wu, J., Liang, S., Bergholz, J. S., He, H., Walsh, E. M., Zhang, Y., & Xiao, Z.-X. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.239 · Cited by 52 · see citing works
Xie, C., Zhu, J., Jiang, Y., Chen, J., Wang, X., Geng, S., Wu, J., Zhong, C., Li, X., & Meng, Z. (2019) · Theranostics · doi:10.7150/thno.33812 · Cited by 52 · see citing works
Yang, R., Liu, N., Chen, L., Jiang, Y., Shi, Y., Mao, C., Liu, Y., Wang, M., Lai, W., Tang, H., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1276-y · Cited by 51 · see citing works
ASPP2 suppresses squamous cell carcinoma via RelA/p65–mediated repression of p63
Tordella, L., Koch, S., Salter, V., Pagotto, A., Doondeea, J. B., Feller, S. M., Ratnayaka, I., Zhong, S., Goldin, R. D., Lozano, G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309362110 · Cited by 48 · see citing works
“Hence,ΔNp63 is considered an oncogene (19).”
Hepatic p63 regulates steatosis via IKKβ/ER stress
Porteiro, B., Fondevila, M. F., Delgado, T. C., Iglesias, C., Imbernón, M., Iruzubieta, P., Crespo, J., Zabala‐Letona, A., Fernø, J., González‐Terán, B., et al. (2017) · Nature Communications · doi:10.1038/ncomms15111 · Cited by 47 · see citing works
Chatterjee, K., Das, P., Chattopadhyay, N. R., Mal, S., & Choudhuri, T. (2019) · Heliyon · doi:10.1016/j.heliyon.2019.e02624 · Cited by 48 · see citing works
“ΔNp63α is observed to induce tumor-initiating stem-like proliferation by cooperating with Ras via interaction with the chromatin remodeling protein Lsh (Keyes et al., 2011).”
BackgroundAlveolar regeneration by airway secretory-cell-derived p63+ progenitors
Lv, Z., Liu, Z., Liu, K., Lin, X., Pu, W., Li, Y., Zhao, H., Xi, Y., Sui, P., Vaughan, A. E., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.08.005 · Cited by 46 · see citing works
DeCastro, A., Dunphy, K. A., Hutchinson, J. A., Balboni, A., Cherukuri, P., Jerry, D. J., & DiRenzo, J. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.37 · Cited by 45 · see citing works
DNA replication timing alterations identify common markers between distinct progeroid diseases
Rivera‐Mulia, J. C., Desprat, R., Trevilla‐García, C., Cornacchia, D., Schwerer, H., Sasaki, T., Sima, J., Fells, T., Studer, L., Lemaı̂tre, J.-M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711613114 · Cited by 45 · see citing works
“Consistently, p63 mice have epidermal developmental defects and a shorter life span (25–28), and TP63 is required for proper skin stratification (29, 30).”
BackgroundTao, Y., Liu, S., Briones, V. R., Geiman, T. M., & Muegge, K. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr611 · Cited by 45 · see citing works
Yamano, S., Gi, M., Tago, Y., Doi, K., Okada, S., Hirayama, Y., Tachibana, H., Ishii, N., Fujioka, M., Tatsumi, K., et al. (2015) · Cancer Science · doi:10.1111/cas.12855 · Cited by 44 · see citing works
CD44 polymorphisms and its variants, as an inconsistent marker in cancer investigations
Gomari, M. M., Farsimadan, M., Rostami, N., Mahmoudi, Z., Fadaie, M., Farhani, I., & Tarighi, P. (2021) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2021.108374 · Cited by 44 · see citing works
Personalized and targeted therapy of esophageal squamous cell carcinoma: an update
Liu, Y., Xiong, Z., Beasley, A., D’Amico, T. A., & Chen, X. L. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13144 · Cited by 42 · see citing works
Sethi, I., Sinha, S., & Buck, M. J. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-1042 · Cited by 40 · see citing works
Increased ACTL6A occupancy within mSWI/SNF chromatin remodelers drives human squamous cell carcinoma
Chang, C.-Y., Shipony, Z., Lin, S. G., Kuo, A., Xiong, X., Loh, K. M., Greenleaf, W. J., & Crabtree, G. R. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.10.005 · Cited by 41 · see citing works
Yang, X., Miao, B., Wei, C., Dong, R., Gao, P., Zhang, X., Lu, J., Gao, C., Wang, X., Sun, H., et al. (2019) · Cancer Science · doi:10.1111/cas.14037 · Cited by 39 · see citing works
p63 cooperates with CTCF to modulate chromatin architecture in skin keratinocytes
Qu, J., Yi, G., & Zhou, H. (2019) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0280-y · Cited by 37 · see citing works
“Furthermore, p63 directly regulates 8 chromatin factors, Satb1, Lsh, and Brg1, to control the chromatin remodelling during epidermis 9 development [9-11].”
BackgroundLiu, N., Yang, R., Shi, Y., Chen, L., Liu, Y., Wang, Z., Liu, S., Ouyang, L., Wang, H., Lai, W., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00249-w · Cited by 40 · see citing works
Lai, W., Jia, J., Yan, B., Jiang, Y., Shi, Y., Chen, L., Mao, C., Liu, X., Tang, H., Gao, M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.22868 · Cited by 39 · see citing works
Wu, H. H., Wang, B., Armstrong, S., Abuetabh, Y., Leng, S., Roa, W., Atfi, A., Marchese, A., Wilson, B. A., Sergi, C. M., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab081 · Cited by 39 · see citing works
Chen, L., Shi, Y., Liu, N., Wang, Z., Yang, R., Yan, B., Liu, X., Lai, W., Liu, Y., Xiao, D., et al. (2019) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0302-9 · Cited by 38 · see citing works
Huang, D., Li, Q., Sun, X., Sun, X., Tang, Y., Qu, Y., Liu, D., Yu, T., Li, G., Tong, T., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00689-5 · Cited by 38 · see citing works
Zhang, Y., Cheng, Y., Ren, X., Hori, T., Huber-Keener, K. J., Zhang, L., Yap, K. L., Liu, D., Shantz, L. M., Qin, Z.-H., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0139 · Cited by 37 · see citing works
The role of microRNAs in stemness of cancer stem cells
Rad, S. M. A. H., Bavarsad, M. S., Arefian, E., Jaseb, K., Shahjahani, M., & Saki, N. (2013) · Oncology Reviews · doi:10.4081/oncol.2013.e8 · Cited by 37 · see citing works
Elevated ΔNp63α Levels Facilitate Epidermal and Biliary Oncogenic Transformation
Devos, M., Gilbert, B., Denecker, G., Leurs, K., Guire, C. M., Lemeire, K., Hochepied, T., Vuylsteke, M., Lambert, J., den Broecke, C. V., et al. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.09.026 · Cited by 37 · see citing works
“Indeed, ΔNp63α is able to block oncogene-induced senescence in keratinocytes by mutated Ras, which results in enhanced malignant conversion when grafted onto nude mice (Ha et al., 2011, Keyes et al., 2011).”
BackgroundEpigenetic regulation of adult stem cell function
Rinaldi, L., & Benitah, S. A. (2014) · FEBS Journal · doi:10.1111/febs.12946 · Cited by 37 · see citing works
Regulation of p63 Protein Stability via Ubiquitin-Proteasome Pathway
Li, C., & Xiao, Z. J. (2014) · BioMed Research International · doi:10.1155/2014/175721 · Cited by 36 · see citing works
ΔNp63α down-regulates c-Myc modulator MM1 via E3 ligase HERC3 in the regulation of cell senescence
Chen, Y., Li, Y., Peng, Y., Zheng, X., Fan, S., Yi, Y., Zeng, P. C., Chen, H., Kang, H. C., Zhang, Y., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0132-5 · Cited by 36 · see citing works
Chromatin regulators in mammalian epidermis
Frye, M., & Benitah, S. A. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.08.009 · Cited by 35 · see citing works
p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer
Smirnov, A., Anemona, L., Novelli, F., Piro, M. C., Annicchiarico‐Petruzzelli, M., Melino, G., & Candi, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225781 · Cited by 35 · see citing works
“Indeed, p63 contributes to cancer development, preventing oncogene-induced senescence of keratinocytes by activating the expression of the chromatin remodeler LSH [53].”
BackgroundTai, G., Ranjzad, P., Marriage, F., Rehman, S., Denley, H., Dixon, J., Mitchell, K., Day, P. J., & Woolf, A. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081167 · Cited by 34 · see citing works
“P63 is essential for epidermal stratification [18,19] and is implicated in skin tomourigenesis [32].”
BackgroundCrosstalk among p53 family members in cutaneous carcinoma
Missero, C., & Antonini, D. (2014) · Experimental Dermatology · doi:10.1111/exd.12320 · Cited by 33 · see citing works
Yu, Y., Morales, J. R., Feng, L., Lee, J. J., El‐Naggar, A. K., & Vigneswaran, N. (2015) · Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · doi:10.1016/j.oooo.2014.12.022 · Cited by 30 · see citing works
The Chromatin Remodeler HELLS: A New Regulator in DNA Repair, Genome Maintenance, and Cancer
Peixoto, E., Khan, A. U., Lewis, Z., Contreras-Galindo, R., & Czaja, W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169313 · Cited by 31 · see citing works
Basenko, E. Y., Kamei, M., Ji, L., Schmitz, R. J., & Lewis, Z. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005790 · Cited by 27 · see citing works
- Authors
- Keyes, W. M., Pecoraro, M., Aranda, V., Vernersson-Lindahl, E., Li, W., Vogel, H., Guo, X., Garcia, E. L., Michurina, T. V., Enikolopov, G., Muthuswamy, S. K., & Mills, A. A.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Universitat Pompeu Fabra (ES)
- Stanford Medicine (US)
- University of Toronto (CA)
- Corresponding author
- Keyes, William M.
- Mills, Alea A.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 8
- Issue
- 2
- Pages
- 164-176
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4373450
- OpenAlex
- W2005062632
- Semantic Scholar
- c1f79d43c5cb2d63b4b44bf6992e804b60c11dd7
- Cited by
- 193
- References
- 53
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 11 · 2023: 8 · 2022: 5 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 13 · 2017: 17 · 2016: 18 · 2015: 6 · 2014: 18 · 2013: 18 · 2012: 17
- FWCI
- 14.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R01CA098830)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- ΔNp63α, p63 isoforms, LSH, chromatin remodeling, oncogenes, senescence bypass, oncogene-induced senescence, skin stem cells, keratin 15, stem cell proliferation, carcinogenesis, stratified epithelium, skin cancer
- MeSH terms
- Animals, Cells, Cultured, DNA Helicases, Flow Cytometry, Humans, Mice, Nude, Phosphoproteins, Protein Binding, Skin, Stem Cells, Trans-Activators, Keratinocytes, Polymerase Chain Reaction, Chromatin Immunoprecipitation, Cell Proliferation, Mice
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