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Cancer Lett. 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.

Author information

1
Case Comprehensive Cancer Center, Division of General Medical Sciences-Oncology, Case Western Reserve University, Wolstein Research Building, 2103 Cornell Road Cleveland, OH 44106, United States.

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

PMID:
23474494
PMCID:
PMC3752409
DOI:
10.1016/j.canlet.2013.02.048
[Indexed for MEDLINE]
Free PMC Article

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