TGF- β signaling in cancer – a double-edged sword
Abstract
Transforming growth factor (TGF) beta1 is a potent growth inhibitor, with tumor-suppressing activity. Cancers are often refractile to this growth inhibition either because of genetic loss of TGF-beta signaling components or, more commonly, because of downstream perturbation of the signaling pathway, such as by Ras activation. Carcinomas often secrete excess TGF-beta1 and respond to it by enhanced invasion and metastasis. Therapeutic approaches should aim to inhibit the TGF-beta-induced invasive phenotype, but also to retain its growth-inhibitory and apoptosis-inducing effects.
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Oncogenes such as RAS might exert cell-nonautonomous protumorigenic effects through nontransformed cells during the process of inducing senescence.
“Thus, oncogenes such as RAS, which are known to activate protumorigenic paracrine mechanisms during transformation [ 59 – 61 ], might also exert cell-nonautonomous protumorigenic effects through nontransformed cells during the process of inducing senescence ( Figure 7 D).”
From Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008) · cites this paper as [61]
Cites
Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O., & Alitalo, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37365-9 · Cited by 694 · see citing works
Cui, W., Fowlis, D. J., Bryson, S., Duffie, E., Ireland, H., Balmain, A., & Akhurst, R. J. (1996) · Cell · doi:10.1016/s0092-8674(00)80127-0 · Cited by 628 · see citing works
Self-citationArteaga, C. L., Hurd, S. D., Winnier, A. R., Johnson, M. D., Fendly, B. M., & Forbes, J. T. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116871 · Cited by 359 · see citing works
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Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721 · see citing works
TGF-β directly targets cytotoxic T cell functions during tumor evasion of immune surveillance
Thomas, D. A., & Massagué, J. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.10.012 · Cited by 1,355 · see citing works
Targeting TGF-β Signaling in Cancer
Colak, S., & ten Dijke, P. (2017) · Trends in cancer · doi:10.1016/j.trecan.2016.11.008 · Cited by 1,003 · see citing works
TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression
Yang, L., Pang, Y., & Moses, H. L. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.04.002 · Cited by 1,023 · see citing works
Yang, L., Huang, J., Ren, X., Gorska, A. E., Chytil, A., Aakre, M., Carbone, D. P., Matrisian, L. M., Richmond, A., Lin, P. C., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2007.12.004 · Cited by 918 · see citing works
Androgen receptor and growth factor signaling cross-talk in prostate cancer cells.
Zhu, M.-L., & Kyprianou, N. (2008) · Endocrine Related Cancer · doi:10.1677/erc-08-0084 · Cited by 286 · see citing works
Grauel, A. L., Nguyen, B., Ruddy, D., Laszewski, T., Schwartz, S., Chang, J., Chen, J., Piquet, M., Pelletier, M., Yan, Z., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19920-5 · Cited by 211 · see citing works
Targeted tumor therapy with the TGF-β2 antisense compound AP 12009
SCHLINGENSIEPEN, K., SCHLINGENSIEPEN, R., STEINBRECHER, A., HAU, P., BOGDAHN, U., FISCHERBLASS, B., & JACHIMCZAK, P. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.09.002 · Cited by 195 · see citing works
Koopman Van Aarsen, L. A., Leone, D. R., Ho, S., Dolinski, B. M., McCoon, P. E., LePage, D. J., Kelly, R., Heaney, G., Rayhorn, P., Reid, C., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2307 · Cited by 146 · see citing works
Laverty, H. G., Wakefield, L. M., Occleston, N. L., O’Kane, S., & Ferguson, M. W. J. (2009) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2009.07.002 · Cited by 110 · see citing works
The tale of transforming growth factor‐beta (TGFβ) signaling: A soigné enigma
Chaudhury, A., & Howe, P. H. (2009) · IUBMB Life · doi:10.1002/iub.239 · Cited by 105 · see citing works
Abdelghany, M. F., El-Sawy, H. B., Abd El-hameed, S. A. A., Khames, M. K., Abdel-Latif, H. M. R., & Naiel, M. A. E. (2020) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2020.10.015 · Cited by 92 · see citing works
HDAC8 cooperates with SMAD3/4 complex to suppress SIRT7 and promote cell survival and migration
Tang, X., Li, G., Su, F., Cai, Y., Shi, L., Meng, Y., Liu, Z., Sun, J., Wang, M., Qian, M., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa039 · Cited by 91 · see citing works
Lescan, M., Perl, R. M., Golombek, S., Pilz, M., Hann, L., Yasmin, M., Behring, A., Keller, T., Nolte, A., Gruhn, F., et al. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.03.013 · Cited by 52 · see citing works
Matters of context guide future research in TGFβ superfamily signaling
Akhurst, R. J., & Padgett, R. W. (2015) · Science Signaling · doi:10.1126/scisignal.aad0416 · Cited by 52 · see citing works
Self-citationIkeda, M., Morimoto, M., Tajimi, M., Inoue, K., Benhadji, K. A., Lahn, M. M. F., & Sakai, D. (2019) · Investigational New Drugs · doi:10.1007/s10637-018-0636-3 · Cited by 46 · see citing works
Flanders, K. C., Yang, Y.-A., Herrmann, M., Chen, J., Mendoza, N., Mirza, A. M., & Wakefield, L. M. (2016) · Oncotarget · doi:10.18632/oncotarget.9416 · Cited by 39 · see citing works
Schmid, S. A., Gaumann, A., Wondrak, M., Eckermann, C., Schulte, S., Mueller-Klieser, W., Wheatley, D. N., & Kunz-Schughart, L. A. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.05.016 · Cited by 26 · see citing works
- Authors
- Akhurst, R. J., & Derynck, R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Akhurst, Rosemary J
- Derynck, Rik
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 11
- Issue
- 11
- Pages
- S44-S51
- ISSN
- 0962-8924 (ISSN-L)
- OpenAlex
- W2018867485
- Cited by
- 756
- References
- 3
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 24 · 2023: 13 · 2022: 14 · 2021: 18 · 2020: 30 · 2019: 43 · 2018: 30 · 2017: 40 · 2016: 34 · 2015: 39 · 2014: 45 · 2013: 31 · 2012: 47
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL060231)
- National Cancer Institute (R01CA063101)
- National Institute of General Medical Sciences (R01GM060514, R01-GM60514-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- TGF-beta signaling, TGF-β1, tumor suppression, tumor invasion, metastasis, Ras activation, apoptosis, cancer therapy, growth inhibition
- MeSH terms
- Animals, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Signal Transduction, Transforming Growth Factor beta, Disease Progression
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