Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium
Open accessAbstract
Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcome among patients with lung cancer bearing similar mutations, suggesting that other pathways are important. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well-defined role in colon and skin cancer; however, its role in lung cancer is unclear. We have shown here that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult mouse lung does not itself promote tumor development. However, concurrent activation of Wnt/β-catenin signaling and expression of a constitutively active Kras mutant (KrasG12D) led to a dramatic increase in both overall tumor number and size compared with KrasG12D alone. Activation of Wnt/β-catenin signaling altered the KrasG12D tumor phenotype, resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This was associated with decreased E-cadherin expression at the cell surface, which may underlie the increased metastasis of tumors with active Wnt/β-catenin signaling. Together, these data suggest that activation of Wnt/β-catenin signaling can combine with other oncogenic pathways in lung epithelium to produce a more aggressive tumor phenotype by imposing an embryonic distal progenitor phenotype and by decreasing E-cadherin expression.
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?
In vitro, PIK3CA mutations that co-occur enhance invasion and migration of cells.
“In vitro, co-occurring PIK3CA mutations promote cellular invasion and migration”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [123]
PIK3CA co-mutations do not appear to affect progression-free survival with first- or second-line EGFR TKI therapy.
“do not appear to impact response rates and progression-free survival with first or second line EGFR TKI therapy73, 115, 123”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [123]
PIK3CA co-mutations do not appear to affect response rates to first- or second-line EGFR TKI therapy.
“do not appear to impact response rates and progression-free survival with first or second line EGFR TKI therapy73, 115, 123”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [123]
Some in vivo studies link co-occurring PIK3CA mutations to poorer overall survival.
“in vivo they are associated with worse overall survival in some studies”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [123]
Response to first-, second-, or third-generation EGFR TKIs appears unaffected by PIK3CA co-mutations.
“co-mutations in PIK3CA don’t impact response to first, second or third generation EGFR TKIs113, 123, 174.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [123]
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
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486 · see citing works
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674 · see citing works
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709 · see citing works
<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368 · see citing works
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237 · see citing works
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338 · see citing works
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681 · see citing works
A molecular mechanism for the effect of lithium on development.
Klein, P. S., & Melton, D. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8455 · Cited by 2,305 · see citing works
Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer
Kim, C. F. B., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., Crowley, D. G., Bronson, R. T., & Jacks, T. (2005) · Cell · doi:10.1016/j.cell.2005.03.032 · Cited by 2,196 · see citing works
The β-Catenin/TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells
van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.-P., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01014-0 · Cited by 2,030 · see citing works
Edwards, B. K., Ward, E., Kohler, B. A., Eheman, C., Zauber, A. G., Anderson, R. N., Jemal, A., Schymura, M. J., Lansdorp‐Vogelaar, I., Seeff, L. C., et al. (2010) · Cancer · doi:10.1002/cncr.24760 · Cited by 2,002 · see citing works
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,877 · see citing works
Jho, E., Zhang, T., Domon–Dell, C., Joo, C., Freund, J., & Costantini, F. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1172-1183.2002 · Cited by 1,683 · see citing works
miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis
Ma, L., Young, J. J., Prabhala, H. K., Pan, E., Mestdagh, P., Muth, D., Teruya‐Feldstein, J., Reinhardt, F., Önder, T. T., Valastyan, S., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2024 · Cited by 1,336 · see citing works
Intestinal polyposis in mice with a dominant stable mutation of the β‐catenin gene
Harada, N., Tamai, Y., Ishikawa, T., Sauer, B., Takaku, K., Oshima, M., & Taketo, M. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.21.5931 · Cited by 1,198 · see citing works
Rawlins, E. L., Okubo, T., Xue, Y., Brass, D. M., Auten, R. L., Hasegawa, H., Wang, F., & Hogan, B. L. M. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.04.002 · Cited by 855 · see citing works
Wnt/β-catenin signaling in cancer stemness and malignant behavior
Fodde, R., & Brabletz, T. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.007 · Cited by 786 · see citing works
Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer
van Haaften, G., Dalgliesh, G. L., Davies, H., Chen, L., Bignell, G., Greenman, C., Edkins, S., Hardy, C., O'Meara, S., Teague, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.349 · Cited by 784 · see citing works
WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis
Nguyen, D. X., Chiang, A. C., Zhang, X. H.-F., Kim, J. Y., Kris, M. G., Ladanyi, M., Gerald, W. L., & Massagué, J. (2009) · Cell · doi:10.1016/j.cell.2009.04.030 · Cited by 622 · see citing works
A common human skin tumour is caused by activating mutations in β-catenin
Chan, E., Gat, U., McNiff, J. M., & Fuchs, E. (1999) · Nature Genetics · doi:10.1038/7747 · Cited by 612 · see citing works
Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma
Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., & Jacks, T. (2009) · Nature · doi:10.1038/nature08462 · Cited by 514 · see citing works
Que, J., Okubo, T., Goldenring, J. R., Nam, K.-T., Kurotani, R., Morrisey, E. E., Taranova, O., Pevny, L., & Hogan, B. L. M. (2007) · Development · doi:10.1242/dev.003855 · Cited by 511 · see citing works
Self-citationBlache, P., van de Wetering, M., Duluc, I., Domon–Dell, C., Berta, P., Freund, J., Clevers, H. C., & Jay, P. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200311021 · Cited by 507 · see citing works
Lu, Y., Thomson, J. M., Wong, H. Y. F., Hammond, S. M., & Hogan, B. L. M. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.08.007 · Cited by 480 · see citing works
Morrisey, E. E., Ip, H. S., Lu, M. M., & Parmacek, M. S. (1996) · Developmental Biology · doi:10.1006/dbio.1996.0165 · Cited by 470 · see citing works
Self-citationGoss, A., Tian, Y., Tsukiyama, T., Cohen, E. D., Zhou, D. D., Lu, M. M., Yamaguchi, T. P., & Morrisey, E. E. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.005 · Cited by 447 · see citing works
Self-citationDiMeo, T. A., Anderson, K., Phadke, P. A., Feng, C. W., Perou, C. M., Naber, S., & Kuperwasser, C. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4135 · Cited by 416 · see citing works
The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells
Rawlins, E. L., Clark, C. P., Xue, Y., & Hogan, B. L. M. (2009) · Development · doi:10.1242/dev.037317 · Cited by 371 · see citing works
von Burstin, J., Eser, S., Paul, M. C., Seidler, B., Brandl, M., Messer, M., von Werder, A., Schmidt, A., Mages, J., Pagel, P., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.004 · Cited by 356 · see citing works
Wnt7b regulates mesenchymal proliferation and vascular development in the lung
Shu, W., Jiang, Y. Q., Lu, M. M., & Morrisey, E. E. (2002) · Development · doi:10.1242/dev.129.20.4831 · Cited by 354 · see citing works
Self-citationClassification of Proliferative Pulmonary Lesions of the Mouse
Nikitin, A. Y., Alcaraz, A., Anver, M. R., Bronson, R. T., Cardiff, R. D., Dixon, D., Fraire, A. E., Gabrielson, E. W., Gunning, W. T., Haines, D. C., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3376 · Cited by 334 · see citing works
Multiple roles for Sox2 in the developing and adult mouse trachea
Que, J., Luo, X., Schwartz, R. J., & Hogan, B. L. M. (2009) · Development · doi:10.1242/dev.034629 · Cited by 322 · see citing works
β-Catenin Is Required for Specification of Proximal/Distal Cell Fate during Lung Morphogenesis
Mucenski, M. L., Wert, S. E., Nation, J. M., Loudy, D. E., Huelsken, J., Birchmeier, W., Morrisey, E. E., & Whitsett, J. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305892200 · Cited by 322 · see citing works
Self-citationShu, W., Guttentag, S. H., Wang, Z., Andl, T., Ballard, P. L., Lu, M. M., Piccolo, S., Birchmeier, W., Whitsett, J. A., Millar, S. E., et al. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.04.014 · Cited by 298 · see citing works
Self-citationA Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration
Zhang, Y., Goss, A., Cohen, E. D., Kadzik, R. S., Lepore, J. J., Muthukumaraswamy, K., Yang, J., DeMayo, F. J., Whitsett, J. A., Parmacek, M. S., et al. (2008) · Nature Genetics · doi:10.1038/ng.157 · Cited by 284 · see citing works
Self-citationThe E-cadherin cell–cell adhesion complex and lung cancer invasion, metastasis, and prognosis
Bremnes, R. M., Veve, R., Hirsch, F. R., & Franklin, W. A. (2002) · Lung Cancer · doi:10.1016/s0169-5002(01)00471-8 · Cited by 246 · see citing works
Okubo, T., Knoepfler, P. S., Eisenman, R. N., & Hogan, B. L. M. (2005) · Development · doi:10.1242/dev.01678 · Cited by 234 · see citing works
β-Catenin/Tcf-regulated transcription prior to the midblastula transition
Yang, J., Tan, C. L., Darken, R. S., Wilson, P. A., & Klein, P. S. (2002) · Development · doi:10.1242/dev.00150 · Cited by 211 · see citing works
Increased prevalence of K-ras oncogene mutations in lung adenocarcinoma
Mills, N. E. (1995) · Lung Cancer · doi:10.1016/0169-5002(95)90161-2 · Cited by 158 · see citing works
GATA6 regulates differentiation of distal lung epithelium
Yang, H., Lu, M. M., Zhang, L., Whitsett, J. A., & Morrisey, E. E. (2002) · Development · doi:10.1242/dev.129.9.2233 · Cited by 149 · see citing works
Self-citationConditional Stabilization ofβ-Catenin Expands the Pool of Lung Stem Cells
Reynolds, S. D., Zemke, A. C., Giangreco, A., Brockway, B., Teisanu, R. M., Drake, J. A., Mariani, T. J., Di, Y. P., Taketo, M. M., & Stripp, B. R. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0053 · Cited by 132 · see citing works
Wnt Inhibitory Factor 1 Decreases Tumorigenesis and Metastasis in Osteosarcoma
Rubin, E. M., Guo, Y., Tu, K., Xie, J., Zi, X., & Hoang, B. H. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0147 · Cited by 132 · see citing works
Thomsen, M. K., Ambroisine, L., Wynn, S. L., Cheah, K. S. E., Foster, C. S., Fisher, G., Berney, D. M., Møller, H., Reuter, V. E., Scardino, P. T., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2370 · Cited by 126 · see citing works
The ras Oncogenes in Human Lung Cancer
Rodenhuis, S., & Slebos, R. J. C. (1990) · American Review of Respiratory Disease · doi:10.1164/ajrccm/142.6_pt_2.s27 · Cited by 121 · see citing works
Shigemitsu, K., Sekido, Y., Usami, N., Mori, S., Sato, M., Horio, Y., Hasegawa, Y., Bader, S. A., Gazdar, A. F., Minna, J. D., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204557 · Cited by 103 · see citing works
Normal lung development and function afterSox9 inactivation in the respiratory epithelium
Perl, A. T., Kist, R., Shan, Z., Scherer, G., & Whitsett, J. A. (2005) · genesis · doi:10.1002/gene.20093 · Cited by 97 · see citing works
Temporal colinearity in expression of anterior hox genes in developing chick embryos
Gaunt, S. J., & Strachan, L. (1996) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199611)207:3 · Cited by 91 · see citing works
SOX9 expression is a general marker of basal cell carcinoma and adnexal‐related neoplasms
Vidal, V., Ortonne, N., & Schedl, A. (2008) · Journal of Cutaneous Pathology · doi:10.1111/j.1600-0560.2007.00815.x · Cited by 91 · see citing works
APC mutations are infrequent but present in human lung cancer
Ohgaki, H. (2003) · Cancer Letters · doi:10.1016/j.canlet.2003.10.020 · Cited by 91 · see citing works
Yin, Z., Gonzales, L. W., Kolla, V., Rath, N., Zhang, Y., Lu, M. M., Kimura, S., Ballard, P. L., Beers, M. F., Epstein, J. A., et al. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00385.2005 · Cited by 83 · see citing works
Self-citationZhang, Y., Rath, N., Hannenhalli, S. S., Wang, Z., Cappola, T. P., Kimura, S., Atochina‐Vasserman, E. N., Lu, M. M., Beers, M. F., & Morrisey, E. E. (2006) · Development · doi:10.1242/dev.02720 · Cited by 80 · see citing works
Self-citationE-cadherin negatively regulates neoplastic growth in non-small cell lung cancer: role of Rho GTPases
Asnaghi, L., Vass, W. C., Quadri, R., Day, P. M., Qian, X., Braverman, R., Papageorge, A. G., & Lowy, D. R. (2010) · Oncogene · doi:10.1038/onc.2010.39 · Cited by 76 · see citing works
Saad, A. G., Yeap, B. Y., Thunnissen, E., Pinkus, G. S., Pinkus, J. L., Loda, M. F., Sugarbaker, D. J., Johnson, B. E., & Chirieac, L. R. (2008) · Cancer · doi:10.1002/cncr.23826 · Cited by 69 · see citing works
Mouse Models of Human Non-Small-Cell Lung Cancer: Raising the BarPreprint
KIM, C. F. B., Jackson, E. L., Kirsch, D. G., Grimm, J., Shaw, A. T., Lane, K. M., Kissil, J. L., Olive, K. P., Sweet-Cordero, A., Weissleder, R., et al. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.037 · Cited by 58 · see citing works
Procopio, A. D., Strizzi, L., Vianale, G., Betta, P., Puntoni, R., Fontana, V., Tassi, G., Gareri, F., & Mutti, L. (2000) · Genes Chromosomes and Cancer · doi:10.1002/1098-2264(2000)9999:9999 · Cited by 52 · see citing works
Homeobox gene HOP has a potential tumor suppressive activity in human lung cancer
Chen, Y., Pacyna-Gengelbach, M., Deutschmann, N., Niesporek, S., & Petersen, I. (2007) · International Journal of Cancer · doi:10.1002/ijc.22753 · Cited by 46 · see citing works
Wang, X.-Q., Li, H. Y., Putten, V. V., Winn, R. A., Heasley, L. E., & Nemenoff, R. A. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-07-0732 · Cited by 46 · see citing works
Cre‐mediated recombination in mouse Clara cells
Li, H., Cho, S. N., Evans, C. M., Dickey, B. F., Jeong, J., & DeMayo, F. J. (2008) · genesis · doi:10.1002/dvg.20396 · Cited by 32 · see citing works
Self-citationRapid and large-scale method to detect K-ras gene mutations in tumor samples
Lopez‐Crapez, E., Chypre, C., Saavedra, J., Marchand, J., & Grenier, J. (1997) · Clinical Chemistry · doi:10.1093/clinchem/43.6.936 · Cited by 28 · see citing works
Reduced Expression of E-cadherin in Human Non-small Cell Lung Carcinoma
Myong, N. (2004) · Cancer Research and Treatment · doi:10.4143/crt.2004.36.1.56 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Sunaga N, Kohno T, Kolligs FT, Fearon ER, Saito R, Yokota J. Constitutive activation of the Wnt signal- ing pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma. Genes Chromosomes Cancer. 2001;30(3):316-321.
- Jen Y, Manova K, Benezra R. Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev Dyn. 1996;207(3):235-252.
Cited by
Sorted by citations
WNT signalling pathways as therapeutic targets in cancer
Anastas, J. N., & Moon, R. T. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3419 · Cited by 1,902 · see citing works
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019 · see citing works
Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells
Nabhan, A. N., Brownfield, D., Harbury, P. B., Krasnow, M. A., & Desai, T. (2018) · Science · doi:10.1126/science.aam6603 · Cited by 731 · see citing works
Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing
Maynard, A., McCoach, C. E., Rotow, J. K., Harris, L., Haderk, F., Kerr, D. L., Yu, E. A., Schenk, E. L., Tan, W., Zee, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.017 · Cited by 697 · see citing works
Wnt Signaling Pathway in Non-Small Cell Lung Cancer
Stewart, D. J. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt356 · Cited by 653 · see citing works
Wnt signaling in stem and cancer stem cells
Holland, J. D., Klaus‐Bergmann, A., Garratt, A. N., & Birchmeier, W. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.01.004 · Cited by 504 · see citing works
The relationship between COPD and lung cancer
Durham, A. L., & Adcock, I. M. (2015) · Lung Cancer · doi:10.1016/j.lungcan.2015.08.017 · Cited by 456 · see citing works
Self-citationRapid modelling of cooperating genetic events in cancer through somatic genome editing
Rivera, F. J. S., Papagiannakopoulos, T. Y., Romero, R., Tammela, T., Bauer, M. R., Bhutkar, A. J., Joshi, N. S., Subbaraj, L., Bronson, R. T., Xue, W., et al. (2014) · Nature · doi:10.1038/nature13906 · Cited by 404 · see citing works
Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells
Testa, U., Castelli, G., & Pelosi, E. (2018) · Cancers · doi:10.3390/cancers10080248 · Cited by 406 · see citing works
“KRAS mutations leads to a more aggressive form of lung cancer with an embryonic progenitor phenotype [229].”
BackgroundInfluentialA Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma
Tammela, T., Rivera, F. J. S., Cetinbas, N. M., Wu, K., Joshi, N. S., Helenius, K. P., Park, Y., Azimi, R., Kerper, N. R., Wesselhoeft, R. A., et al. (2017) · Nature · doi:10.1038/nature22334 · Cited by 338 · see citing works
Jang, G.-B., Kim, J. Y., Cho, S., Park, K., Jung, J., Lee, H., Hong, I., & Nam, J. (2015) · Scientific Reports · doi:10.1038/srep12465 · Cited by 330 · see citing works
microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1
Wang, H., Tan, Z., Hu, H., Liu, H., Wu, T., Zheng, C., Wang, X., Luo, Z., Wang, J., Liu, S., et al. (2019) · BMC Cancer · doi:10.1186/s12885-019-5951-3 · Cited by 304 · see citing works
WNT as a Driver and Dependency in Cancer
Parsons, M. J., Tammela, T., & Dow, L. E. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0190 · Cited by 257 · see citing works
Satoh, H., Moriguchi, T., Takai, J., Ebina, M., & Yamamoto, M. P. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4499 · Cited by 251 · see citing works
Common stemness regulators of embryonic and cancer stem cells
Hadjimichael, C. (2015) · World Journal of Stem Cells · doi:10.4252/wjsc.v7.i9.1150 · Cited by 246 · see citing works
Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis
Zhang, Y., Morris, J. P., Yan, W., Schofield, H. K., Gurney, A. L., Simeone, D. M., Millar, S. E., Hoey, T., Hebrok, M., & di Magliano, M. P. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4384 · Cited by 207 · see citing works
Vaz, M. J., Hwang, S. Y., Kagiampakis, I., Phallen, J. A., Patil, A., O’Hagan, H. M., Murphy, L. M., Zahnow, C. A., Gabrielson, E., Velculescu, V. E., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.08.006 · Cited by 186 · see citing works
“It is also suggested that KRAS mutations alone are not a strong predictor for developing lung cancer, but associated increases in WNT signaling accelerate lung tumorigenesis (Pacheco-Pinedo et al., 2011; Pacheco-Pinedo and Morrisey, 2011).”
Wnt signaling in lung development, regeneration, and disease progression
Aros, C. J., Pantoja, C. J., & Gomperts, B. N. (2021) · Communications Biology · doi:10.1038/s42003-021-02118-w · Cited by 166 · see citing works
Chen, S., Xu, Y., Chen, Y., Li, X., Mou, W., Wang, L., Liu, Y., Reisfeld, R. A., Xiang, R., Lv, D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036326 · Cited by 160 · see citing works
Vadlakonda, L., Pasupuleti, M., & Reddanna, P. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00085 · Cited by 159 · see citing works
“Pacheco-Pinedo et al. (2011) recently demonstrated that cooperation between K-Ras mutant and the Wnt/β-catenin signaling is the cause of aggressive lung tumor phenotype.”
BackgroundTargeting the WNT Signaling Pathway in Cancer Therapeutics
Tai, D. W.-M., Wells, K. R., Arcaroli, J. J., Vanderbilt, C., Aisner, D. L., Messersmith, W. A., & Lieu, C. H. (2015) · The Oncologist · doi:10.1634/theoncologist.2015-0057 · Cited by 159 · see citing works
McCubrey, J. A., Rakus, D., Gizak, A., Steelman, L. S., Abrams, S. L., Lertpiriyapong, K., Fitzgerald, T. L., Yang, L. V., Montalto, G., Cervello, M., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.09.004 · Cited by 149 · see citing works
Kwon, M.-C., & Berns, A. J. M. (2013) · Molecular Oncology · doi:10.1016/j.molonc.2013.02.010 · Cited by 145 · see citing works
“In addition, concurrent activation of Wnt/beta-Catenin signaling and mutant Kras signaling leads to aggressive and highly proliferative distal lung tumor formation (Pacheco-Pinedo et al., 2011).”
BackgroundCheung, W. K. C., Zhao, M., Liu, Z. Z., Stevens, L. E., Cao, P. D., Fang, J. E., Westbrook, T. F., & Nguyen, D. X. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.04.009 · Cited by 140 · see citing works
“In DASC-like tumors, the expression of WNT inhibitory factor 1 (WIF1), an antagonist of the canonical WNT pathway (Clevers, 2006), was suppressed (Figure S1C), consistent with hyperactive WNT/TCF signaling being a mediator of lung ADC progression and metastasis (Nguyen et al., 2009; Pacheco-Pinedo et al., 2011).”
BackgroundMelotti, A., Mas, C., Kuciak, M., Lorente‐Trigos, A., Borges, I., & Altaba, A. R. I. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201404084 · Cited by 130 · see citing works
“Ivermectin inhibits lung cancer xenograft growth in vivo Beyond colon cancer, WNT-TCF signaling has been implicated in a number of other tumor types including advanced non-small cell lung cancer (Nguyen et al, 2009; Pacheco-Pinedo et al, 2011).”
BackgroundWNT signaling – lung cancer is no exception
Rapp, J., Járomi, L., Kvell, K., Miskei, G., & Pongracz, J. E. (2017) · Respiratory Research · doi:10.1186/s12931-017-0650-6 · Cited by 113 · see citing works
“Also, if down-regulation of SOX2 and upregulation of SOX9 and GATA6 simultaneously accompany KRAS mutation [51] then alterations in WNT signaling do not modulate the final outcome [48].”
BackgroundCell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation
Phillips, S. M., Prat, A., Sedic, M., Proia, T. A., Wronski, A., Mazumdar, S., Skibinski, A., Shirley, S. H., Perou, C. M., Gill, G., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.03.008 · Cited by 108 · see citing works
“By doing so, these cells acquire properties that make them amenable to cancer initiation (Pacheco-Pinedo et al., 2011; Proia et al., 2011; Schwitalla Ste et al., 2013; Youssef et al., 2010, 2012).”
BackgroundZheng, D., Limmon, G. V., Yin, L., Leung, N. H. N., Yu, H., Chow, V. T. K., & Chen, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048451 · Cited by 96 · see citing works
TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10
Tan, P., Ye, Y., He, L., Xie, J., Ji, J., Ma, G., Pan, H., Han, L., Han, W., & Zhou, Y. (2018) · PLoS Biology · doi:10.1371/journal.pbio.3000051 · Cited by 95 · see citing works
β-Catenin Contributes to Lung Tumor Development Induced by EGFR Mutations
Nakayama, S., Sng, N., Carretero, J., Welner, R. S., Hayashi, Y., Yamamoto, M., Tan, A. J., Yamaguchi, N., Yasuda, H., Li, D., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0184 · Cited by 91 · see citing works
“Given that expression of an activated β-catenin alone causes lung tumors in none (47) or only a small subset of mice (49), it is predicted that tumor initiation likely requires concomitant genetic alterations in addition to activation of Wnt/β-catenin signaling.”
Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells
Wuputra, K., Ku, C., Wu, D., Lin, Y., Saito, S., & Yokoyama, K. K. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01584-0 · Cited by 100 · see citing works
Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells
Trejo‐Solís, C., Escamilla-Ramírez, Á., Jiménez‐Farfán, D., Castillo‐Rodríguez, R. A., Flores‐Nájera, A., & Cruz-Salgado, A. (2021) · Pharmaceuticals · doi:10.3390/ph14090871 · Cited by 90 · see citing works
“The overexpression of β-catenin in lung cancer cells does not induce lung tumors in mice, while the co-expression of β-catenin and the KRAS onco-gene results in lung and melanoma tumors [15,16].”
BackgroundPharmacological modulation of beta‐catenin and its applications in cancer therapy
Thakur, R. K., & Mishra, D. P. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12033 · Cited by 89 · see citing works
Cancer cells remodel themselves and vasculature to overcome the endothelial barrier
Shenoy, A. K., & Lu, J. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.10.031 · Cited by 87 · see citing works
Molecular Determinants of Lung Development
Morrisey, E. E., Cardoso, W. V., Lane, R. H., Rabinovitch, M., Abman, S. H., Ai, X., Albertine, K. H., Bland, R. D., Chapman, H. A., Checkley, W., et al. (2013) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201207-036ot · Cited by 86 · see citing works
Self-citationXu, X., Cui, J., Wang, H., Ma, L., Zhang, X., Guo, W., Xue, X., Wang, Y., Qiu, S., Tian, X., et al. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100503 · Cited by 85 · see citing works
“Although modern technology has greatly improved the efficacy of lung cancer treatment over the last decade, five-year survival rates are still only approximately 10%–20% [2].”
BackgroundNovel insight into the function of tankyrase (Review)
Kim, M. K. (2018) · Oncology Letters · doi:10.3892/ol.2018.9551 · Cited by 84 · see citing works
“The Wnt pathway is also involved in lung cancer (50 , 51), and therefore antagonizing the Wnt pathway through tankyrase inhibition could be effective against lung cancer.”
Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer
Azbazdar, Y., Karabicici, M., Erdal, E., & Özhan, G. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.631623 · Cited by 83 · see citing works
Opposing role of Notch1 and Notch2 in a KrasG12D-driven murine non-small cell lung cancer model
Baumgart, A., Mazur, P. K., Anton, M., Rudelius, M., Schwamborn, K., Feuchtinger, A., Behnke, K., Walch, A. K., Braren, R., Peschel, C., et al. (2014) · Oncogene · doi:10.1038/onc.2013.592 · Cited by 83 · see citing works
Evidence for tankyrases as antineoplastic targets in lung cancer
Busch, A. M., Johnson, K. C., Stan, R. V., Sanglikar, A., Ahmed, Y. F., Dmitrovsky, E., & Freemantle, S. J. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-211 · Cited by 81 · see citing works
“The Wnt pathway is known to contribute to lung cancer progression [8,68] and also to metastasis [9].”
BackgroundLanfredini, S., Thapa, A., & O’Neill, E. E. (2019) · Biochemical Society Transactions · doi:10.1042/bst20170521 · Cited by 78 · see citing works
Bryant, J. L., Britson, J. S., Balko, J. M., Willian, M. C., Timmons, R. B., Frolov, A., & Black, E. P. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.465 · Cited by 79 · see citing works
“Ontological annotation of the 13 signature genes and their potential targets revealed enrichment in components of EMT, including Wnt pathway signalling, which may partially explain the ability of the signature to segregate metastatic tumours (Pacheco-Pinedo et al, 2011).”
BackgroundLi, Z., Wang, Y., Li, Y., Yin, W., Mo, L., Qian, X., Zhang, Y., Wang, G., Bu, F., Zhang, Z., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0451-y · Cited by 79 · see citing works
Stem Cells and Cell Therapies in Lung Biology and Diseases: Conference Report
Weiss, D. J., Bates, J. H. T., Gilbert, T. W., Liles, W. C., Lutzko, C., Rajagopal, J., & Prockop, D. J. (2013) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201304-089aw · Cited by 79 · see citing works
Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness
Gong, X., Yi, J., Carmon, K. S., Crumbley, C., Xiong, W., Thomas, A., Fan, X., Guo, S., An, Z., Chang, J. T., et al. (2014) · Oncogene · doi:10.1038/onc.2014.417 · Cited by 76 · see citing works
Juan, J. M., Muraguchi, T., Iezza, G., Sears, R. C., & McMahon, M. (2014) · Genes & Development · doi:10.1101/gad.233627.113 · Cited by 75 · see citing works
“Key unresolved questions in this model are as follows: (1) What promotes an initiated BRAF-expressing lung epithelial cell to become a benign lung tumor? (2) What triggers the senescence-like proliferative arrest of BRAF-induced benign tumors? (3) Does bypass of senescence inevitably result in malignant progression to…”
BackgroundResultInfluentialLu, Y., Wei, C., & Xi, Z. (2014) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-014-9779-5 · Cited by 71 · see citing works
“imposing an embryonic distal progenitor phenotype on lung epithelium (Pacheco-Pinedo et al. 2011).”
BackgroundInfluentialKe, Z., He, W., Lai, Y., Guo, X., Chen, S., Li, S., Wang, Y., & Wang, L. (2014) · Oncotarget · doi:10.18632/oncotarget.2421 · Cited by 70 · see citing works
“During the early progression of metastasis, activation of the Wnt/β-catenin pathway may promote the migration and invasion of cancer cells by upregulating matrix metalloproteinases MMP-7 and MMP-26 and down-regulating cell-cell contact protein E-cadherin [10–13].”
BackgroundLineage factors and differentiation states in lung cancer progression
Cheung, W. K. C., & Nguyen, D. X. (2015) · Oncogene · doi:10.1038/onc.2015.85 · Cited by 69 · see citing works
Wang, I., Snyder, J. E., Zhang, Y., Lander, J. M., Nakafuku, Y., Lin, J. A., Chen, G., Kalin, T. V., Whitsett, J. A., & Kalinichenko, V. V. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00355-12 · Cited by 66 · see citing works
“In contrast to our findings in developing respiratory epithelium, recent studies demonstrate that Wnt/ -catenin synergizes with oncogenic Kras to induce lung tumors in adult mice (37).”
ResultChristensen, J., Bentz, S., Sengstag, T., Shastri, V. P., & Anderle, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060051 · Cited by 66 · see citing works
LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells
Wei, Q., Chen, Z.-H., Wang, L., Zhang, T., Duan, L., Behrens, C., Wistuba, I. I., Minna, J. D., Gao, B., Luo, J.-H., et al. (2015) · Oncogene · doi:10.1038/onc.2015.328 · Cited by 62 · see citing works
Xie, C., Liang, C., Wang, R., Yi, K., Zhou, X., Li, X., Chen, Y., Miao, D., Zhong, C., & Zhu, J. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109211 · Cited by 57 · see citing works
Hou, M., Cheng, Z., Shen, H., He, S., Yang, L., Pan, Y., Feng, C., Chen, X., Zhang, Y., Lin, M., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5358 · Cited by 56 · see citing works
“The Wnt/β-catenin pathway is reported to be involved in EMT by decreasing the cellcell contact protein E-cadherin to promote the migration and invasion of cancer cells [5, 6].”
Wnt signaling pathway: Implications for therapy in lung cancer and bone metastasis
Xi, Y., & Chen, Y. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.07.010 · Cited by 56 · see citing works
Zhou, C., Zhu, X., Liu, N., Dong, X., Zhang, X., Huang, H., Tang, Y., Liu, S., Hu, M., Wang, M., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01268-5 · Cited by 54 · see citing works
“Overexpression of constitutively active β-catenin produces no lung tumor, whereas co-expression of constitutively active forms of both KRAS and β-catenin induces lung tumors, as shown in one model of lung cancer.(22) Expression of constitutively active β-catenin also synergizes with the active forms of NRAS to induce…”
BackgroundWNT/β-catenin regulatory roles on PD-(L)1 and immunotherapy responses
Mortezaee, K. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-023-01274-z · Cited by 54 · see citing works
“WNT/β-catenin reduces the expression of epithe-lial-related markers, such as E-cadherin [40], which is for acquisition of cancer stemness features.”
BackgroundPotent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes
Guimarães, P. P. G., Tan, M., Tammela, T., Wu, K., Chung, A., Oberli, M. A., Wang, K., Spektor, R., Riley, R., Viana, C. T. R., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.09.025 · Cited by 54 · see citing works
“Wnt signaling is essential for the initiation and maintenance of Braf-driven lung adenomas in mice [5], and forced activation of this pathway promotes progression of Kras or Braf mutant lung tumors [5,6].”
BackgroundThe Role of Sox Genes in Lung Morphogenesis and Cancer
Zhu, Y., Li, Y., Wei, J., & Liu, X. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131215767 · Cited by 53 · see citing works
“Additionally, a recent work demonstrated that a combinatoral activation of both canonical Wnt signaling and Kras pathway showed a remarkable increase of lung cancer formation with a more progenitor-like phenotype [102,103].”
BackgroundArya, N., Sardana, V., Saxena, M. T., Rangarajan, A., & Katti, D. S. (2012) · Journal of The Royal Society Interface · doi:10.1098/rsif.2012.0564 · Cited by 53 · see citing works
WNT AGONIST ATTENUATES LIVER INJURY AND IMPROVES SURVIVAL AFTER HEPATIC ISCHEMIA/REPERFUSION
Kuncewitch, M., Yang, W.-L., Molmenti, E. P., Nicastro, J. M., Coppa, G. F., & Wang, P. (2012) · Shock · doi:10.1097/shk.0b013e3182764fe8 · Cited by 51 · see citing works
“However, the activation of Wnt/"-catenin signaling has been linked to tumorigenesis (30).”
BackgroundOta, C., Ng-Blichfeldt, J.-P., Korfei, M., Alsafadi, H. N., Lehmann, M., Skrońska-Wąsek, W., Santis, M. M. D., Günther, A., Wagner, D. E., & Königshoff, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-31214-x · Cited by 49 · see citing works
Liu, Z., Sun, B., Qi, L., Li, Y., Zhao, X., Zhang, D., & Zhang, Y. H. (2014) · Histopathology · doi:10.1111/his.12474 · Cited by 47 · see citing works
Investigating regulated signaling pathways in therapeutic targeting of non-small cell lung carcinoma
Alam, M., Hasan, G. M., Eldin, S. M., Adnan, M., Riaz, M. B., Islam, A., Khan, I., & Hassan, M. I. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114452 · Cited by 48 · see citing works
Bleckmann, A., Siam, L., Klemm, F., Rietkötter, E., Wegner, C., Krämer, F., Beißbarth, T., Binder, C. R., Stadelmann, C., & Pukrop, T. (2012) · Clinical & Experimental Metastasis · doi:10.1007/s10585-012-9552-7 · Cited by 46 · see citing works
“Moreover, constitutively active KRAS and b-catenin in the peripheral Clara cells lead to more aggressive adenocarcinomas by inducing a switch to an embryonic progenitor phenotype, indicating a role of b-catenin in the peripheral cells [29].”
Winn, R. A., Sechler, Cizmic, Avasarala, Scoyk, V., Brzezinski, Bikkavilli, & Kelley (2013) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s26058 · Cited by 45 · see citing works
“119 Therefore, attempts to use this pathway as a target for therapeutic gain have all been focused on inhibiting canonical signaling.”
KRAS(G12D) drives lepidic adenocarcinoma through stem-cell reprogramming
Juul, N. H., Yoon, J.-K., Martinez, M. C., Rishi, N., Kazadaeva, Y. I., Morri, M., Neff, N. F., Trope, W., Shrager, J. B., Sinha, R., et al. (2023) · Nature · doi:10.1038/s41586-023-06324-w · Cited by 46 · see citing works
Botting, G. M., Rastogi, I., Chhabra, G., Nlend, M., & Puri, N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0136155 · Cited by 44 · see citing works
Multidimensional Roles of Collagen Triple Helix Repeat Containing 1 (CTHRC1) in Malignant Cancers
Jiang, N., Cui, Y., Liu, J., Zhu, X., Wu, H., Yang, Z., & Ke, Z. (2016) · Journal of Cancer · doi:10.7150/jca.16539 · Cited by 42 · see citing works
“In previous reports, the tumor microenvironment of extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT), which are significantly related to the aggressive feature of cancer cells [12, 16-18], has been suggested to be mediated by CTHRC1 [12, 15].”
BackgroundXu, Q., Wang, C., Zhou, J., Xu, Z.-M., Gao, J., Sui, P., Walsh, C. P., Ji, H., & Xu, G. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2107599119 · Cited by 41 · see citing works
Decreased Expression of SOX7 is Correlated with Poor Prognosis in Lung Adenocarcinoma Patients
Li, B., Ge, Z., Song, S., Zhang, S., Yan, H., Huang, B., & Zhang, Y. (2012) · Pathology & Oncology Research · doi:10.1007/s12253-012-9542-8 · Cited by 41 · see citing works
PIK3CAH1047R Accelerates and Enhances KRASG12D-Driven Lung Tumorigenesis
Green, S., Trejo, C. L., & McMahon, M. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1249 · Cited by 38 · see citing works
Ustiyan, V., Zhang, Y., Perl, A. T., Whitsett, J. A., Kalin, T. V., & Kalinichenko, V. V. (2016) · Developmental Dynamics · doi:10.1002/dvdy.24393 · Cited by 39 · see citing works
“, 2012); however, these signaling pathways synergize to stimulate lung carcinogenesis in adult mice (Pacheco-Pinedo et al., 2011).”
BackgroundSOX9 maintains human foetal lung tip progenitor state by enhancing WNT and RTK signalling
Sun, D., Llora Batlle, O., van den Ameele, J., Thomas, J. C., He, P., Lim, K., Tang, W., Xu, C., Meyer, K. B., Teichmann, S. A., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022111338 · Cited by 38 · see citing works
“Lung adenocarcinomas often take on an embryonic progenitor phenotype (Pacheco-Pinedo et al , 2011; Laughney et al , 2020).”
Zhang, X., Lou, Y., Wang, H., Zheng, X., Dong, Q., Sun, J., & Han, B. (2015) · Medical Oncology · doi:10.1007/s12032-014-0462-1 · Cited by 37 · see citing works
Kim, M., Suh, Y., Oh, J., Lee, B., Kim, J., & Jang, S. J. (2016) · Scientific Reports · doi:10.1038/srep32770 · Cited by 37 · see citing works
Fang, Z., Han, X., Chen, Y., Tong, X., Xue, Y., Yao, S., Tang, S., Pan, Y., Sun, Y., Wang, X., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01227-0 · Cited by 35 · see citing works
The possible role of Wnt/β‐catenin signalling in vitiligo treatment
Lin, X., Meng, X., & Lin, J. (2023) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.19022 · Cited by 36 · see citing works
“88 Abnormal activation of Wnt/β-catenin signalling is often observed in patients with colorectal cancer.”
BackgroundSkeletal metastasis: treatments, mouse models, and the Wnt signaling
Valkenburg, K. C., Steensma, M. R., Williams, B. O., & Zhong, Z. A. (2013) · 癌症：英文版 · doi:10.5732/cjc.012.10218 · Cited by 35 · see citing works
“Lung tumorigenesis is also associated with up-regulated Wnt signaling([123-126]).”
BackgroundFang, B. (2015) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmv090 · Cited by 35 · see citing works
“However, the progression to highly invasive and metastatic cancers is dramatically enhanced by the presence of mutations in other cancer driver genes, including defects in Tp53 [53–55], Stk11 [56–58], Ink4a/Arf [53,59], Smad4 [60], Pten [61], Tgfbr2 [62], and Runx3 [63]; and activation of Wnt/beta-catenin signaling [6…”
P120-catenin regulates pulmonary fibrosis and TGF-β induced lung fibroblast differentiation
Zhang, Y., Jiao, H., Wu, Y., & Sun, X. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.05.052 · Cited by 35 · see citing works
Phosphorylation of p300 increases its protein degradation to enhance the lung cancer progression
Wang, S., Hung, C.-Y., Chuang, J., Chang, W., Hsu, T., & Hung, J. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.02.001 · Cited by 35 · see citing works
Pan, F., Shen, F., Yang, L., Zhang, L., Guo, W., & Tian, J. (2018) · Oncology Letters · doi:10.3892/ol.2018.8790 · Cited by 34 · see citing works
Hirata, E., Ichikawa, T., Horike, S., & Kiyokawa, E. (2018) · Cancer Science · doi:10.1111/cas.13816 · Cited by 33 · see citing works
National Heart, Lung, and Blood Institute Workshop
Robbins, I. M., Moore, T. M., Blaisdell, C. J., & Abman, S. H. (2012) · Circulation · doi:10.1161/circulationaha.112.092924 · Cited by 33 · see citing works
Wnt and Kras signaling-dark siblings in lung cancer
Pacheco-Pinedo, E. C., & Morrisey, E. E. (2011) · Oncotarget · doi:10.18632/oncotarget.305 · Cited by 33 · see citing works
“Taking advantage of cell lineage specific cre lines for the secretory epithelium of the upper airways (CC10cre, [10]), we recently showed that while activation of β-catenin alone using the Ctnnb1Δ(ex3) mice which will delete important regulatory phosphorylation sites within β-catenin that inhibit its function in Wnt s…”
BackgroundSelf-citationA novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy
Hsu, T., Chen, Y., Hung, C.-Y., Wang, Y.-C., Lin, S.-J., Su, W., Lai, M.-D., Kim, S. Y., Wang, Q., Qian, K., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3701 · Cited by 32 · see citing works
“In addition, we found that SYK023 (5 μM) effectively decreased the expression of some proteins that promote lung tumor formation (Supplementary Figure 7B), including N-cadherin, β-catenin, vimentin, and c-myc [32-35].”
BackgroundAn integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer
Wang, H., Lv, Q., Xu, Y., Cai, Z., Zheng, J., Cheng, X., Dai, Y., Janne, P. A., Ambrogio, C., & Köhler, J. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.10.012 · Cited by 31 · see citing works
Widespread Repression of Gene Expression in Cancer by a Wnt/β-Catenin/MAPK Pathway
Harmston, N., Lim, J. Y. S., Arqués, O., Pálmer, H. G., Petretto, E. G., Virshup, D. M., & Madan, B. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2129 · Cited by 31 · see citing works
“For example, in experimental models of lung carcinogenesis, Morrisey and coworkers found that stabilization of b-catenin markedly accelerated KRAS(G12D)-induced tumorigenesis (51).”
BackgroundA Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent
Yeh, C., Su, C., Huang, C. F., Lin, J. K.-Y., Lee, W., Chang, P. M., Kuo, Y.-L., Liu, Y.-W., Wang, L.-S., Wu, C., et al. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/910451 · Cited by 31 · see citing works
Thapa, R., Magar, A. T., Shrestha, J., Panth, N., Idrees, S., Sadaf, T., Bashyal, S., Elwakil, B. H., Sugandhi, V. V., Rojekar, S. V., et al. (2024) · MedComm · doi:10.1002/mco2.70018 · Cited by 32 · see citing works
written on behalf of the AME Lung Cancer Collaborative Group, Jin, J., Zhan, P., Katoh, M., Kobayashi, S. S., Phan, K. H., Qian, H., Li, H., Wang, X., Wang, X., et al. (2017) · Translational Lung Cancer Research · doi:10.21037/tlcr.2017.02.07 · Cited by 29 · see citing works
HOPX: A Unique Homeodomain Protein in Development and Tumor Suppression
Gokulan, R. C., Yap, L. F., & Paterson, I. C. (2022) · Cancers · doi:10.3390/cancers14112764 · Cited by 29 · see citing works
Chang, Y.-X., Lin, Y., Chen, C., Huang, M., Hsiao, M., & Liang, P. (2020) · Cancers · doi:10.3390/cancers12123865 · Cited by 28 · see citing works
“Wnt / β -catenin signaling can combine with other oncogenic pathways in the lung epithelium to produce a more aggressive tumor phenotype by inducing an embryonic distal progenitor phenotype and by decreasing E-cadherin expression [50].”
BackgroundCosimelli, B., Laneri, S., Ostacolo, C., Sacchi, A., Severi, E., Porcù, E., Rampazzo, E., Moro, E., Basso, G., & Viola, G. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.05.071 · Cited by 27 · see citing works
“All of the reported mutations result in an upregulated Wnt signaling [39,40].”
BackgroundAHNAK suppresses ovarian cancer progression through the Wnt/β-catenin signaling pathway
Cai, Y., Hu, Y., Yu, F., Tong, W., Wang, S., Sheng, S., & Zhu, J. (2021) · Aging · doi:10.18632/aging.203473 · Cited by 26 · see citing works
Natural compounds: Wnt pathway inhibitors with therapeutic potential in lung cancer
Shen, X., Gao, C., Li, H., Liu, C., Wang, L., Li, Y., Liu, R., Sun, C., & Zhuang, J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1250893 · Cited by 25 · see citing works
CTHRC1 affects malignant tumor cell behavior and is regulated by miR-30e-5p in human prostate cancer
Ma, Z., Chao, F., Wang, S., Song, Z., Zhuo, Z., Zhang, J., Xu, G., & Chen, G. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.02.098 · Cited by 25 · see citing works
ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesisPreprint
Wang, L., Yang, H., Zamperone, A., Diolaiti, D., Palmbos, P. L., Abel, E. V., Purohit, V., Dolgalev, I., Rhim, A. D., Ljungman, M. E., et al. (2019) · Genes & Development · doi:10.1101/gad.323303.118 · Cited by 24 · see citing works
“…factor are required for SOX9 expression in epithelial cells (Blache et al. 2004), and several reports have indicated that SOX9 expression is associated with β -catenin signaling in bladder, lung, colon, and ovarian tumorigenesis (Blache et al. 2004; Ahmad et al. 2011; Pacheco-Pinedo et al. 2011).”
Guo, W., Shen, F., Xiao, W., Chen, J., & Pan, F. (2017) · Oncology Letters · doi:10.3892/ol.2017.7100 · Cited by 23 · see citing works
“One potential therapeutic target for lung cancer is the Wnt signaling pathway (4-7).”
Background
- Authors
- Pacheco-Pinedo, E. C., Durham, A. C., Stewart, K. M., Goss, A. M., Lu, M. M., DeMayo, F. J., & Morrisey, E. E.
- Affiliations
- University of Pennsylvania (US)
- Baylor College of Medicine (US)
- Corresponding author
- Morrisey, Edward E.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-05-02
- Volume
- 121
- Issue
- 5
- Pages
- 1935-1945
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3083778
- OpenAlex
- W2074358850
- Cited by
- 164
- References
- 60
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 17 · 2021: 7 · 2020: 13 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 5 · 2015: 17 · 2014: 17 · 2013: 18 · 2012: 11
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL087825, R01HL064632, HL064632, HL087825)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- Wnt/β-catenin signaling, lung carcinogenesis, KRAS G12D, KRAS mutation, bronchiolar epithelium, E-cadherin, metastasis, lung cancer, mouse lung
- MeSH terms
- Animals, Bronchi, Cell Membrane, Epithelial Cells, Humans, Lung, Lung Neoplasms, Mice, Transgenic, Mutation, Phenotype, Stem Cells, Signal Transduction, Cadherins, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Wnt Proteins, Mice
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
