| First Author | Morrison CD | Year | 2013 |
| Journal | Cancer Lett | Volume | 341 |
| Issue | 1 | Pages | 30-40 |
| PubMed ID | 23474494 | Mgi Jnum | J:202800 |
| Mgi Id | MGI:5521460 | Doi | 10.1016/j.canlet.2013.02.048 |
| Citation | Morrison CD, et al. (2013) The relevance of the TGF-beta Paradox to EMT-MET programs. Cancer Lett 341(1):30-40 |
| abstractText | The role of transforming growth factor-beta (TGF-beta) 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-beta function is known as the "TGF-beta 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-beta, 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-beta 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-beta 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. |
