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

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.

• Authors: Chevaun D Morrison, Jenny G Parvani, William P Schiemann
• Journal: Cancer letters (Cancer Lett) Vol. 341 Issue 1 Pg. 30-40 (Nov 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23474494 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Bone Morphogenetic Proteins
• DNA-Binding Proteins
• ERP29 protein, human
• GRHL2 protein, human
• Heat-Shock Proteins
• Integrins
• MIRN200 microRNA, human
• MicroRNAs
• Transcription Factors
• Transforming Growth Factor beta
• Proto-Oncogene Proteins c-abl

Topics

• Alternative Splicing
• Animals
• Bone Morphogenetic Proteins (metabolism)
• Cell Hypoxia
• DNA-Binding Proteins (metabolism)
• Epithelial-Mesenchymal Transition (physiology)
• Fibroblasts (metabolism, pathology)
• Heat-Shock Proteins (metabolism)
• Humans
• Integrins (metabolism)
• MicroRNAs (genetics, metabolism)
• Neoplasms (genetics, metabolism, pathology)
• Neoplastic Stem Cells (metabolism, pathology)
• Proto-Oncogene Proteins c-abl (metabolism)
• Signal Transduction
• Transcription Factors (metabolism)
• Transforming Growth Factor beta (genetics, metabolism)