Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells
Open accessAbstract
The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kinome. Two known Ras-regulated kinases were identified, phosphoinositide 3-kinase p110alpha and ribosomal protein S6 kinase p70(S6K1), plus the MAP kinase kinase kinase kinase MINK, which had not previously been implicated in Ras signaling. MINK is activated after Ras induction via a mechanism involving reactive oxygen species and mediates stimulation of the stress-activated protein kinase p38 MAPK downstream of the Raf/ERK pathway. p38 MAPK activation is essential for Ras-induced p21(WAF1/CIP1) upregulation and cell cycle arrest. MINK is thus a distal target of Ras signaling in the induction of a growth-arrested, senescent-like phenotype that may act to oppose oncogenic transformation in HOSE cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ras-induced senescence can be inhibited by using antioxidants or growing cells in low-oxygen conditions.
“Ras-induced senescence can be inhibited by using antioxidants or growing cells in low-oxygen conditions (8, 25, 33, 51).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [33]
The section “Ras-Induced Reactive Oxygen Species Promote Activation of MINK and p38 MAPK” reports that antioxidant NAC inhibited Ras-induced ROS and the appearance of senescent morphology in human ovarian surface epithelial cells. It does not report that growing cells in low-oxygen conditions inhibits Ras-induced senescence; the Introduction mentions oxygen-rich culture only as part of a debate about oncogene-induced arrest. The antioxidant result concerns senescent morphology and signaling, not a demonstrated reversal of permanent growth arrest. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 4× · see citing works
“It therefore appears that inducible expression of Ras leads to a growth arrest in this ovarian epithelial cell system by a mechanism that does not involve either p53 or p16, the two pathways most commonly associated with oncogene-induced growth arrest (Lloyd et al., 1997; Serrano et al., 1997; Sewing et al., 1997).”
BackgroundInfluentialTargeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,262 · see citing works
Self-citationSenescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · cited 2× · see citing works
“…the PI 3-kinase inhibitor LY294002 has previously been reported to block hydrogen peroxide-induced senescence in human diploid fibroblasts (Wang et al., 2004) and PTEN deletion has recently been associated with induction of p53-dependent senescence in mouse prostate glands (Chen et al., 2005).”
BackgroundCreation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345 · see citing works
Self-citationBRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160 · see citing works
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993 · see citing works
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954 · see citing works
Self-citationMitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts
Irani, K., Xia, Y., Zweier, J. L., Sollott, S. J., Der, C. J., Fearon, E. R., Sundaresan, M., Finkel, T., & Goldschmidt-Clermont, P. J. (1997) · Science · doi:10.1126/science.275.5306.1649 · Cited by 1,588 · 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 · see citing works
Lowe, S. W., Cepero, E., & Evan, G. I. (2004) · Nature · doi:10.1038/nature03098 · Cited by 1,309 · see citing works
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220 · see citing works
Rodriguez‐Viciana, P., Warne, P. H., Khwaja, A., Marte, B. M., Pappin, D., Das, P., Waterfield, M. D., Ridley, A. J., & Downward, J. (1997) · Cell · doi:10.1016/s0092-8674(00)80226-3 · Cited by 1,063 · see citing works
Self-citationA large-scale RNAi screen in human cells identifies new components of the p53 pathway
Berns, K., Hijmans, E. M., Mullenders, J., Brummelkamp, T. R., Velds, A., Heimerikx, M., Kerkhoven, R. M., Madiredjo, M., Nijkamp, W., Weigelt, B., et al. (2004) · Nature Cell Biology · doi:10.1038/nature02371 · Cited by 1,059 · see citing works
Self-citationPDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase
Chung, J., Grammar, T. C., Lemon, K. P., Kazlauskas, A., & Blenis, J. (1994) · Nature · doi:10.1038/370071a0 · Cited by 719 · see citing works
A resource for large-scale RNA-interference-based screens in mammals
Paddison, P. J., Silva, J. M., Conklin, D. S., Schlabach, M., Li, M. Z., Aruleba, S., Balija, V. S., O'Shaughnessy, A., Gnoj, L., Scobie, K., et al. (2004) · Nature Cell Biology · doi:10.1038/nature02370 · Cited by 695 · see citing works
Ras Proteins Induce Senescence by Altering the Intracellular Levels of Reactive Oxygen Species
Lee, A. C., Fenster, B. E., Ito, H., Takeda, K., Bae, N. S., Hirai, T., Yu, Z.-X., Ferrans, V. J., Howard, B. H., & Finkel, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7936 · Cited by 691 · see citing works
Hydrogen Peroxide: A Key Messenger That Modulates Protein Phosphorylation Through Cysteine Oxidation
Rhee, S. G., Bae, Y. S., Lee, S.-R., & Kwon, J. (2000) · Science s STKE · doi:10.1126/stke.2000.53.pe1 · Cited by 646 · see citing works
The Ste20 group kinases as regulators of MAP kinase cascades
Dan, I., Watanabe, N. M., & Kusumi, A. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)01980-8 · Cited by 629 · see citing works
A Genetic Screen for Candidate Tumor Suppressors Identifies REST
Westbrook, T. F., Martin, E. S., Schlabach, M. R., Leng, Y., Liang, A. C. T., Feng, B., Zhao, J. J., Roberts, T. M., Mandel, G., Hannon, G. J., et al. (2005) · Cell · doi:10.1016/j.cell.2005.03.033 · Cited by 487 · see citing works
High-Intensity Raf Signal Causes Cell Cycle Arrest Mediated by p21 Cip1
Sewing, A., Wiseman, B. S., Lloyd, A. C., & Land, H. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5588 · Cited by 455 · see citing works
Putting the stress on senescence
Serrano, M., & Blasco, M. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00278-7 · Cited by 413 · see citing works
Mitogen‐activated protein kinase p38 defines the common senescence‐signalling pathway
Iwasa, H., Han, J., & Ishikawa, F. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00620.x · Cited by 388 · see citing works
Wang, W., Chen, J. X., Liao, R., Deng, Q., Zhou, J. J., Huang, S., & Sun, P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.10.3389-3403.2002 · Cited by 376 · see citing works
Opposing Effects of Ras on p53
Ries, S., Biederer, C., Woods, D., Shifman, O., Shirasawa, S., Sasazuki, T., McMahon, M., Oren, M., & McCormick, F. (2000) · Cell · doi:10.1016/s0092-8674(00)00123-9 · Cited by 357 · see citing works
Identification of Modulators of TRAIL-Induced Apoptosis via RNAi-Based Phenotypic Screening
Aza‐Blanc, P., Cooper, C. L., Wagner, K., Batalov, S., Deveraux, Q. L., & Cooke, M. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00348-4 · Cited by 339 · see citing works
p38 MAP Kinase's Emerging Role as a Tumor Suppressor
Bulavin, D. V., & Fornace, A. J. (2004) · Advances in cancer research · doi:10.1016/s0065-230x(04)92005-2 · Cited by 290 · see citing works
A Genetic Screen Identifies PITX1 as a Suppressor of RAS Activity and Tumorigenicity
Kolfschoten, I., van Leeuwen, B., Berns, K., Mullenders, J., Beijersbergen, R. L., Bernards, R., Voorhoeve, P. M., & Agami, R. (2005) · Cell · doi:10.1016/j.cell.2005.04.017 · Cited by 273 · see citing works
Self-citationImmortalization and transformation of primary human airway epithelial cells by gene transfer
Lundberg, A., Randell, S., Stewart, S. A., Elenbaas, B., Hartwell, K. A., Brooks, M., Fleming, M., Olsen, J., Miller, S., Weinberg, R., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205550 · Cited by 267 · see citing works
Cooperating oncogenes converge to regulate cyclin/cdk complexes.Preprint
Lloyd, A. C., Obermüller, F., Staddon, S., Barth, C. F., McMahon, M., & Land, H. (1997) · Genes & Development · doi:10.1101/gad.11.5.663 · Cited by 224 · see citing works
Tsao, S., Mok, S. C., Fey, E. G., Fletcher, J. A., Wan, T. S. K., Chew, E. C., Muto, M. G., KNAPP, R. C., & Berkowitz, R. S. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1184 · Cited by 201 · see citing works
Regulation of cellular response to oncogenic and oxidative stress by Seladin-1
Wu, C., Miloslavskaya, I., Demontis, S., Maestro, R., & Galaktionov, K. I. (2004) · Nature · doi:10.1038/nature03173 · Cited by 191 · see citing works
Deng, Q.-D., Liao, R., Wu, B.-L., & Sun, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308644200 · Cited by 188 · see citing works
Bulavin, D. V., Kovalsky, O., Hollander, M. C., & Fornace, A. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.11.3859-3871.2003 · Cited by 161 · see citing works
Haq, R., Brenton, J. D., Takahashi, M. T., Finan, D., Finkielsztein, A., Damaraju, S., Rottapel, R. K., & Zanke, B. W. (2002) · PubMed · Cited by 143 · see citing works
Mok, S. C., Chan, W. Y., Wong, K., Muto, M. G., & Berkowitz, R. S. (1996) · PubMed · Cited by 136 · see citing works
Downward, J. (2004) · BMJ · doi:10.1136/bmj.328.7450.1245 · Cited by 112 · see citing works
Self-citationPruitt, K., Pruitt, W. M., Bilter, G. K., Westwick, J. K., & Der, C. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203964200 · Cited by 84 · see citing works
Haddad, J. J., Safieh‐Garabedian, B., Saadé, N. E., Kanaan, S. A., & Land, S. C. (2001) · Cytokine · doi:10.1006/cyto.2000.0789 · Cited by 75 · see citing works
Bosch, E., Cherwinski, H. M., Peterson, D., & McMahon, M. (1997) · Oncogene · doi:10.1038/sj.onc.1201270 · Cited by 74 · see citing works
Dan, I., Watanabe, N. M., Kobayashi, T., Suzuki, K., Fukagaya, Y., Kajikawa, E., Kimura, W., Nakashima, T. M., Matsumoto, K., Ninomiya‐Tsuji, J., et al. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01247-3 · Cited by 71 · see citing works
Shields, J. M., Mehta, H., Pruitt, K., & Der, C. J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2304-2317.2002 · Cited by 61 · see citing works
H-, K- and N-Ras inhibit myeloid leukemia cell proliferation by a p21WAF1-dependent mechanism
Delgado, M. D., Vaque, J. P., Arozarena, I., Lopez-Ilasaca, M. A., Martínez, C., Crespo, P., & León, J. (2000) · Oncogene · doi:10.1038/sj.onc.1203384 · Cited by 55 · see citing works
Wang, Y., Meng, A., & Zhou, D. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.04.012 · Cited by 53 · see citing works
Use of RNA interference libraries to investigate oncogenic signalling in mammalian cells
Downward, J. (2004) · Oncogene · doi:10.1038/sj.onc.1208073 · Cited by 51 · see citing works
Self-citationΔMEKK3:ER* activation induces a p38α/β2-dependent cell cycle arrest at the G2 checkpoint
Garner, A. P., Weston, C. R., Todd, D. E., Balmanno, K., & Cook, S. J. (2002) · Oncogene · doi:10.1038/sj.onc.1206000 · Cited by 50 · see citing works
Self-citationThe Significance of p16INK4a in Cell Defences Against Transformation
Drayton, S., Brookes, S., Rowe, J., & Peters, G. G. (2004) · Cell Cycle · doi:10.4161/cc.3.5.837 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
“, 2006), and occurs in a variety of cell types (Lloyd et al., 1997; Nicke et al., 2005; Denoyelle et al., 2006).”
BackgroundThe essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity
Lee, S., Rauch, J., & Kölch, W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031102 · Cited by 807 · see citing works
Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA
Coelho, M. A., de Carné Trécesson, S., Rana, S., Zecchin, D., Moore, C., Molina-Arcas, M., East, P., Spencer-Dene, B., Nye, E., Barnouin, K., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.11.016 · Cited by 653 · see citing works
Self-citationElgendy, M., Sheridan, C., Brumatti, G., & Martin, S. J. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.02.009 · Cited by 426 · see citing works
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · see citing works
p38α MAP Kinase as a Sensor of Reactive Oxygen Species in Tumorigenesis
Dolado, I., Swat, A., Ajenjo, N., Vita, G. D., Cuadrado, A., & Nebreda, Á. R. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.12.013 · Cited by 404 · see citing works
High-throughput RNAi screening in cultured cells: a user's guide
Echeverri, C. J., & Perrimon, N. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1836 · Cited by 380 · see citing works
Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular Senescence
Adams, P. D. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.021 · Cited by 326 · see citing works
Lu, T., & Finkel, T. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.011 · Cited by 327 · see citing works
Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence
Xu, Y., Li, N., Xiang, R., & Sun, P. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.04.004 · Cited by 282 · see citing works
Weyemi, U., Lagente-Chevallier, O., Boufraqech, M., Prenois, F., Courtin, F., Caillou, B., Talbot, M., Dardalhon, M., Al Ghuzlan, A., Bidart, J.-M., et al. (2012) · Oncogene · doi:10.1038/onc.2011.327 · Cited by 285 · see citing works
BRAFE600 in benign and malignant human tumours
Michaloglou, C., Vredeveld, L. C. W., Mooi, W. J., & Peeper, D. S. (2007) · Oncogene · doi:10.1038/sj.onc.1210704 · Cited by 272 · see citing works
The pathways to tumor suppression via route p38
Han, J., & Sun, P. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.06.007 · Cited by 268 · see citing works
Reactive oxygen species: A double-edged sword in oncogenesis
Pan, J., Hong, M., & Ren, J. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.1702 · Cited by 225 · see citing works
p38α MAPK pathway: A key factor in colorectal cancer therapy and chemoresistance
Grossi, V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i29.9744 · Cited by 213 · see citing works
Inflammatory signaling and cellular senescence
Ren, J., Pan, J., Lu, Y.-P., Sun, P., & Han, J. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.10.011 · Cited by 149 · see citing works
RASSF6 is a novel member of the RASSF family of tumor suppressors
Allen, N. P. C., Donninger, H., Vos, M. D., Eckfeld, K., Hesson, L. B., Gordon, L. E., Birrer, M. J., Latif, F., & Clark, G. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210440 · Cited by 142 · see citing works
shRNA libraries and their use in cancer genetics
Bernards, R., Brummelkamp, T. R., & Beijersbergen, R. L. (2006) · Nature Methods · doi:10.1038/nmeth921 · Cited by 140 · see citing works
Self-citationA kinase shRNA screen links LATS2 and the pRB tumor suppressorPreprint
Tschöp, K., Conery, A. R., Litovchick, L., DeCaprio, J. A., Settleman, J. E., Harlow, E., & Dyson, N. J. (2011) · Genes & Development · doi:10.1101/gad.2000211 · Cited by 125 · see citing works
Alternative splicing of SYK regulates mitosis and cell survival
Prinos, P., Garneau, D., Lucier, J., Gendron, D., Couture, S., Boivin, M., Brosseau, J., Lapointe, E., Thibault, P., Durand, M., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2040 · Cited by 114 · see citing works
Oncogene-induced senescence: From biology to therapy
Zhu, H., Blake, S., Kusuma, F. K., Pearson, R. B., Kang, J., & Chan, K. T. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111229 · Cited by 116 · see citing works
Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism
Lin, W., Shen, P., Song, Y., Huang, Y., & Tu, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.635021 · Cited by 97 · see citing works
Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells
Su, C., Johnson, M. E., Torres, A., Thomas, R. M., Manduchi, E., Sharma, P. K., Mehra, P., Coz, C. L., Leonard, M. E., Lu, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17089-5 · Cited by 91 · see citing works
p38α and p38γ Mediate Oncogenic ras-induced Senescence through Differential Mechanisms
Kwong, J., Hong, L., Liao, R., Deng, Q., Han, J., & Sun, P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808327200 · Cited by 82 · see citing works
Hyodo, T., Ito, S., Hasegawa, H., Asano, E., Maeda, M., Urano, T., Takahashi, M., Hamaguchi, M., & Senga, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.372342 · Cited by 81 · see citing works
Ras regulation of DNA-methylation and cancer
Patra, S. K. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.012 · Cited by 80 · see citing works
Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
Fu, G., Xu, Q., Qiu, Y., Jin, X., Xu, T., Dong, S., Wang, J., Ke, Y., Hu, H., Cao, X., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161120 · Cited by 63 · see citing works
The p38‐activated ER stress‐ATF6α axis mediates cellular senescence
Kim, H. S., Kim, Y.-J., Lim, M. J., Park, Y.-G., Park, S. I., & Sohn, J. (2018) · The FASEB Journal · doi:10.1096/fj.201800836r · Cited by 61 · see citing works
Smad inhibition by the Ste20 kinase Misshapen
Kaneko, S., Chen, X., Lu, P., Yao, X., Wright, T. G., Rajurkar, M., Kariya, K., Mao, J., Ip, Y. T., & Xu, L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104128108 · Cited by 60 · see citing works
Kimura, J., Nguyen, S. T., Liu, H., Taira, N., Miki, Y., & Yoshida, K. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn506 · Cited by 58 · see citing works
Chromosomal instability and transcriptome dynamics in cancer
Stevens, J. B., Horne, S. D., Abdallah, B. Y., Ye, C. J., & Heng, H. H. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9428-6 · Cited by 51 · see citing works
LIN, Z.-H., Wang, L., Zhang, J., Liu, Y., Li, X., Guo, L., ZHANG, B., Zhu, W., & Ye, Q. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2455 · Cited by 49 · see citing works
Zheng, H., Seit‐Nebi, A. S., Han, X., Aslanian, A., Tat, J., Liao, R., Yates, J. R., & Sun, P. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.013 · Cited by 49 · see citing works
ZRF1 is a novel S6 kinase substrate that drives the senescence programme
Barilari, M., Bonfils, G., Treins, C., Koka, V., Villeneuve, D. D., Fabrega, S., & Pende, M. (2017) · The EMBO Journal · doi:10.15252/embj.201694966 · Cited by 47 · see citing works
The role of p38 MAPK pathway in p53 compromised state and telomere mediated DNA damage response
Roy, S., Roy, S., Rana, A., Akhter, Y., Hande, M. P., & Banerjee, B. (2018) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2018.05.018 · Cited by 46 · see citing works
CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment
Scheiblecker, L., Kollmann, K., & Sexl, V. (2020) · Pharmaceuticals · doi:10.3390/ph13120418 · Cited by 47 · see citing works
Watanabe, T., Tsuda, M., Tanaka, S., Ohba, Y., Kawaguchi, H., Majima, T., Sawa, H., & Minami, A. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0064 · Cited by 46 · see citing works
Sudbery, I. M., Enright, A. J., Fraser, A. G., & Dunham, I. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-175 · Cited by 46 · see citing works
Leong, S. Y., Ong, B. K. T., & Chu, J. J. H. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004686 · Cited by 45 · see citing works
Swanton, C., Larkin, J., Gerlinger, M., Eklund, A. C., Howell, M. T., Stamp, G., Downward, J., Gore, M. E., Futreal, P. A., Escudier, B. J., et al. (2010) · Genome Medicine · doi:10.1186/gm174 · Cited by 45 · see citing works
Self-citationYue, M., Luo, D., Yu, S., Liu, P., Zhou, Q., Hu, M., Liu, Y., Wang, S., Huang, Q., Niu, Y., et al. (2015) · Blood · doi:10.1182/blood-2015-07-659185 · Cited by 45 · see citing works
Priming of NLRP3 inflammasome activation by Msn kinase MINK1 in macrophages
Zhu, K., Jin, X., Chi, Z., Chen, S., Wu, S., Sloan, R. D., Lin, X., Neculai, D., Wang, D., Hu, H., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00761-1 · Cited by 43 · see citing works
MAP4K3 modulates cell death via the post-transcriptional regulation of BH3-only proteins
Lam, D., Dickens, D., Reid, E. B., Loh, S. H. Y., Moisoi, N., & Martins, L. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900608106 · Cited by 42 · see citing works
Silencing of STRN 4 suppresses the malignant characteristics of cancer cells
Wong, M., Hyodo, T., Asano, E., Funasaka, K., Miyahara, R., Hirooka, Y., Goto, H., Hamaguchi, M., & Senga, T. (2014) · Cancer Science · doi:10.1111/cas.12541 · Cited by 41 · see citing works
Multiplexing siRNAs to compress RNAi-based screen size in human cells
Martin, S. E., Jones, T. L., Thomas, C. L., Lorenzi, P. L., Nguyen, D. A., Runfola, T., Gunsior, M., Weinstein, J. N., Goldsmith, P. K., Lader, E., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm141 · Cited by 40 · see citing works
Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway
Zhu, R., Ji, X., Wu, X., Chen, J., Li, X., Jiang, H., Fu, H., Wang, H., Lin, Z., Tang, X., et al. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.08.005 · Cited by 38 · see citing works
Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence
Ma, J., Hu, X., Liao, C., Xiao, H., Zhu, Q., Li, Y., Liu, Z., Tao, A., He, Z., Xu, C., et al. (2019) · Molecules · doi:10.3390/molecules24061054 · Cited by 33 · see citing works
High-throughput approaches to dissecting MAPK signaling pathways
Friedman, A. A., & Perrimon, N. (2006) · Methods · doi:10.1016/j.ymeth.2006.05.002 · Cited by 33 · see citing works
A primer on using pooled shRNA libraries for functional genomic screens
Hu, G., & Luo, J. (2012) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmr116 · Cited by 32 · see citing works
Wang, H., Song, X., Logsdon, C. D., Zhou, G., Evans, D. B., Abbruzzese, J. L., Hamilton, S. R., Tan, T., & Wang, H. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-1751 · Cited by 32 · see citing works
Zhang, J., Lei, H., & Li, X. (2021) · Environmental Toxicology · doi:10.1002/tox.23361 · Cited by 31 · see citing works
Regulation of Tumorigenesis by p38α MAP Kinase
Dolado, I., & Nebreda, Á. R. (2007) · Springer eBooks · doi:10.1007/4735_2007_0245 · Cited by 31 · see citing works
Sasaki, T., Oga, T., Nakagaki, K., Sakai, K., Sumida, K., Hoshino, K., Miyawaki, I., Saito, K., Suto, F., & Ichinohe, N. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.01.024 · Cited by 30 · see citing works
Armeni, T., Ercolani, L., Urbanelli, L., Magini, A., Magherini, F., Pugnaloni, A., Piva, F., Modesti, A., Emiliani, C., & Principato, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052151 · Cited by 28 · see citing works
Low RASSF6 expression in pancreatic ductal adenocarcinoma is associated with poor survival
Ye, H. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i21.6621 · Cited by 27 · see citing works
p38α limits the contribution of MAP17 to cancer progression in breast tumors
Guijarro, M. V., Vergel, M., Marín, J., Muñoz-Galván, S., Ferrer, I., y Cajal, S. R., Roncador, G., Blanco‐Aparicio, C., & Carnero, A. (2012) · Oncogene · doi:10.1038/onc.2011.619 · Cited by 27 · see citing works
Wang, Y., Cui, R., Zhang, X., Qiao, Y., Liu, X., Chang, Y.-F., Yu, Y., Sun, F., & Wang, J. (2016) · Oncotarget · doi:10.18632/oncotarget.7022 · Cited by 27 · see citing works
Basic Properties of the p38 Signaling Pathway in Response to Hyperosmotic Shock
Messaoud, N. B., Katzarova, I., & López, J. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135249 · Cited by 25 · see citing works
Dominguez‐Villar, M., Muñoz-Suano, A., Baz, B. A., Aguilar, S., Ruiz, J. P. N., Giron, J. A., Rodríguez‐Iglesias, M., & Garcia-Cozar, F. J. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0507335 · Cited by 25 · see citing works
ERK1/2 and p38 cooperate to delay progression through G1 by promoting cyclin D1 protein turnover
Densham, R. M., Todd, D. E., Balmanno, K., & Cook, S. J. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.07.005 · Cited by 22 · see citing works
Self-citationReactive Oxygen Species as Signaling Molecules
Rovira, I. I., & Finkel, T. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-420-9_16 · Cited by 19 · see citing works
Genes and pathways involved in senescence bypass identified by functional genetic screens
Roupakia, E., Markopoulos, G. S., & Kolettas, E. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111432 · Cited by 18 · see citing works
Xu, L., Wang, L., Yang, R., Li, T., & Zhu, X. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad052 · Cited by 17 · see citing works
Yu, D., Hu, J., Sheng, Z., Fu, G., Wang, Y., Chen, Y., Pan, Z., Zhang, X., Wu, Y., Sun, H. X., et al. (2019) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2019.09.009 · Cited by 16 · see citing works
Li, A. X., Martin, T. A., Lane, J., & Jiang, W. G. (2023) · Cancers · doi:10.3390/cancers16010076 · Cited by 15 · see citing works
Agonistic and Antagonistic Roles for TNIK and MINK in Non-Canonical and Canonical Wnt Signalling
Mikryukov, A. A., & Moss, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043330 · Cited by 15 · see citing works
Schouest, K. R., KURASAWA, Y., Furuta, T., Hisamoto, N., Matsumoto, K., & Schumacher, J. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007450 · Cited by 15 · see citing works
Age-dependent regulation of antioxidant genes by p38α MAPK in the liver
Pérez, S., Rius‐Pérez, S., Tormos, A. M., Finamor, I., Nebreda, Á. R., Taléns‐Visconti, R., & Sastre, J. (2018) · Redox Biology · doi:10.1016/j.redox.2018.02.017 · Cited by 15 · see citing works
The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis
Xu, G., Yang, Z., Ding, Y., Liu, Y., Zhang, L., Wang, B., Tang, M., Jing, T., Jiao, K., Xu, X., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01964-6 · Cited by 15 · see citing works
Berger, K. L., Barriga, F., Lace, M. J., Turek, L. P., Zamba, G., Domann, F. E., Lee, J. H., & Klingelhutz, A. J. (2006) · Virology · doi:10.1016/j.virol.2006.07.039 · Cited by 14 · see citing works
Jaśkiewicz, K., Maleszka-Kurpiel, M., Kabza, M., Karolak, J. A., & Gajęcka, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1197054 · Cited by 13 · see citing works
Bantle, C. M., French, C. T., Cummings, J. E., Sadasivan, S., Tran, K., Slayden, R. A., Smeyne, R. J., & Tjalkens, R. B. (2021) · PLoS ONE · doi:10.1371/journal.pone.0245171 · Cited by 13 · see citing works
Expanding the repertoire of RNA interference screens for developing new anticancer drug targets
Haney, S. A. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.11.1429 · Cited by 13 · see citing works
RNAi Applications in Target Validation
Kourtidis, A., Eifert, C., & Conklin, D. S. (2007) · Springer eBooks · doi:10.1007/978-3-540-31339-7_1 · Cited by 13 · see citing works
Ding, B., Li, J., Yan, J.-L., Jiang, C., Qian, L.-B., & Pan, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1515605 · Cited by 11 · see citing works
MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities
Bunardi, C. S., Yeom, M., Kosasih, P., Han, H., Wang, W., & Seo, G. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01544-8 · Cited by 11 · see citing works
A defective splicing machinery promotes senescence through MDM4 alternative splicing
Deschênes, M., Durand, M., Olivier, M., Pellerin‐Viger, A., Rodier, F., & Chabot, B. (2024) · Aging Cell · doi:10.1111/acel.14301 · Cited by 9 · see citing works
Yeh, S., Chen, S., & Chen, B. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00117 · Cited by 10 · see citing works
TNIK: A redox sensor in endothelial cell permeability
Joachim, J., Maselli, D., Petsolari, E., Aman, J., Swiatlowska, P., Killock, D., Chaudhry, H., Zarban, A. A., Sarker, M. H., Fraser, P. A., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk6583 · Cited by 9 · see citing works
Wang, J., Song, L., Yang, S., Zhang, W., Lu, P., Li, S., Li, H., & Wang, L. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7131 · Cited by 9 · see citing works
Kot, A., Koszewska, D., Ochman, B., & Świętochowska, E. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46120826 · Cited by 8 · see citing works
Dokla, E. M. E., Mahmoud, A. H., Elsayed, M., El‐Khatib, A. H., Linscheid, M. W., & Abouzid, K. A. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049284 · Cited by 8 · see citing works
Zhao, C.-S., Huang, D., Peng, T., Huang, M., Xie, C., Chen, J., Kong, J.-R., Xie, R.-C., Liu, Y., & Wang, W. (2017) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2017.03.026 · Cited by 8 · see citing works
Long, X., Steurer, B., Wong, C. W., Kozlova, E., Naumov, V., Pun, F. W., Aliper, A., Ren, F., & Zhavoronkov, A. A. (2024) · Future Medicine AI · doi:10.2217/fmai-2023-0019 · Cited by 4 · see citing works
Cattani‐Cavalieri, I., Li, Y., Margolis, J., Bogard, A. S., Roosan, M. R., & Ostrom, R. S. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1149063 · Cited by 4 · see citing works
(2006) · Nature reviews. Cancer · doi:10.1038/nrc1791 · Cited by 4 · see citing works
Su, C., Johnson, M. E., Torres, A., Thomas, R. M., Manduchi, E., Sharma, P. K., Coz, C. L., Leonard, M. E., Lu, S., Hodge, K. M., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.20.885426 · Cited by 3 · see citing works
Expression and functional validation of new p38α transcriptional targets in tumorigenesis
Swat, A., Dolado, I., Igea, A., Goméz-López, G., Pisano, D. G., Cuadrado, A., & Nebreda, Á. R. (2011) · Biochemical Journal · doi:10.1042/bj20101410 · Cited by 2 · see citing works
Drug target discovery using retroviruses
Blø, M., Micklem, D., & Lorens, J. B. (2007) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2.10.1285 · Cited by 2 · see citing works
Induction of Cellular Senescence: Role of Mitogen-Activated Protein Kinase-Interacting Kinase 1
Ziaei, S., & Shimada, N. (2013) · Springer eBooks · doi:10.1007/978-94-007-7726-2_12 · Cited by 1 · see citing works
Design and Application of a shRNA-Based Gene Replacement Retrovirus
Zhang, R., Adams, P. D., & Ye, X. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-547-3_12 · Cited by 1 · see citing works
Oncogenic RAS Signalling Promotes Tumour Immunoresistance by Stabilising PD-L1 mRNA
Coelho, M. (2017) · UCL Discovery (University College London) · Cited by 1 · see citing works
Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies
Kim, Y. (2014) · Scholarship@Western (Western University)
Costa, M. N. (2009) · UNM’s Digital Repository (University of New Mexico)
Analysis of senescence-like growth arrest induced by RUNX1 and its fusion derived oncoproteins
Wolyniec, K. (2008) · Enlighten: Theses (The University of Glasgow) · doi:10.5525/gla.thesis.578
Porquet, M. Z. (2010) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Oncogene-Induced Senescence (OIS) as a Cellular Response to Oncogenic Stresses
Bourdeau, V., & Ferbeyre, G. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1075-2_3
- Authors
- Nicke, B., Bastien, J., Khanna, S. J., Warne, P. H., Cowling, V., Cook, S. J., Peters, G., Delpuech, O., Schulze, A., Berns, K., Mullenders, J., Beijersbergen, R. L., Bernards, R., Ganesan, T. S., Downward, J., & Hancock, D. C.
- Affiliations
- Cancer Research UK (GB)
- Babraham Institute (GB)
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Downward, Julian
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 20
- Issue
- 5
- Pages
- 673-685
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2067838259
- Cited by
- 108
- References
- 47
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 4 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 6
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Cancer Research UK
- KWF Kankerbestrijding
- Biotechnology and Biological Sciences Research Council (BBS/E/B/0000C199, BBS/E/B/0000H457)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- mink, oncogenic Ras, ovarian surface epithelial cells, p21, growth arrest, p38 MAPK, RAF/ERK pathway, reactive oxygen species, senescence, oncogenic transformation, S6K1, cell cycle arrest
- MeSH terms
- Cell Cycle, Cell Transformation, Neoplastic, Epithelial Cells, Female, Humans, Ovarian Neoplasms, Phenotype, Signal Transduction, Proto-Oncogene Proteins p21(ras), Protein Serine-Threonine Kinases, Reactive Oxygen Species, MAP Kinase Kinase Kinases, Saccharomyces cerevisiae Proteins, RNA Interference, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
