Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Nov 28;341(1):30-40.
doi: 10.1016/j.canlet.2013.02.048. Epub 2013 Mar 5.

The relevance of the TGF-β Paradox to EMT-MET programs

Chevaun D Morrison  1 , Jenny G Parvani, William P Schiemann
Affiliations
Review

The relevance of the TGF-β Paradox to EMT-MET programs

Chevaun D Morrison et al. Cancer Lett. .

Abstract

The role of transforming growth factor-β (TGF-β) during tumorigenesis is complex and paradoxical, reflecting its ability to function as a tumor suppressor in normal and early-stage cancers, and as a tumor promoter in their late-stage counterparts. The switch in TGF-β function is known as the "TGF-β Paradox," whose manifestations are intimately linked to the initiation of epithelial-mesenchymal transition (EMT) programs in developing and progressing carcinomas. Indeed, as carcinoma cells emerge from EMT programs stimulated by TGF-β, they readily display a variety of acquired phenotypes that provide a selective advantage to growing carcinomas, including (i) enhanced cell migration and invasion; (ii) heightened resistance to cytotoxic agents, targeted chemotherapeutic, and radiation treatments; and (iv) boosted expansion of cancer-initiating and stem-like cell populations that underlie tumor metastasis and disease recurrence. At present, the molecular, cellular, and microenvironmental mechanisms that enable post-EMT and metastatic carcinoma cells to hijack the oncogenic activities of TGF-β remain incompletely understood. Additionally, the molecular mechanisms that counter EMT programs and limit the aggressiveness of late-stage carcinomas, events that transpire via mesenchymal-epithelial transition (MET) reactions, also need to be further elucidated. Here we review recent advances that provide new insights into how TGF-β promotes EMT programs in late-stage carcinoma cells, as well as how these events are balanced by MET programs during the development and metastatic progression of human carcinomas.

Keywords: Epithelial plasticity; Metastasis; TGF-β.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1
Schematic of TGF-β and BMP signaling pathways coupled to EMT and MET programs, respectively. TGF-β and BMP signaling systems typically oppose one another in normal epithelial cells. Shown are the receptors for TGF-β and BMP ligands, as well as their downstream effectors operant in mediating the initiation of EMT (TGF-β) and MET (BMP) reactions in normal and malignant cells. ALK-1 is primarily expressed on endothelial cells and functions to regulate proliferation, migration and angiogenesis. The precise signaling components required to mediate these physiological effects remain to be fully elucidated. See text for additional details.
Figure 2
Figure 2
Cell and environmental factors coupled to the induction of EMT and MET programs in carcinoma cells. Activation of TGF-β and BMP signaling systems couples to a complex cascade of expression and repression that is regulated by a variety of factors both within the carcinoma cells themselves, and within their accompanying host microenvironment. Targets of TGF-β and BMP signaling include microRNAs, infiltrating immune cells, and numerous microenvironmental factors and cytokines. Finally, transitioning carcinoma cells further fine tune the balance between EMT:MET reactions through employment of alternative gene splicing events, which gives rise to isoform specific expression of proteins in epithelial versus mesenchymal cell states. See text for additional details.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Massague J. TGFβ in Cancer. Cell. 2008;134:215–230. - PMC - PubMed
    1. Taylor MA, Lee YH, Schiemann WP. Role of TGF-β and the tumor microenvironment during mammary tumorigenesis. Gene Expr. 2011;15:117–132. - PMC - PubMed
    1. Wendt MK, Tian M, Schiemann WP. Deconstructing the mechanisms and consequences of TGF-β-induced EMT during cancer progression. Cell and tissue research. 2012;347:85–101. - PMC - PubMed
    1. Tian M, Neil JR, Schiemann WP. Transforming growth factor-β and the hallmarks of cancer. Cell Signal. 2011;23:951–962. - PMC - PubMed
    1. Taylor MA, Parvani JG, Schiemann WP. The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-β in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia. 2010;15:169–190. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources