| First Author | Shirakihara T | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 4 | Pages | 783-95 |
| PubMed ID | 21224849 | Mgi Jnum | J:169126 |
| Mgi Id | MGI:4939879 | Doi | 10.1038/emboj.2010.351 |
| Citation | Shirakihara T, et al. (2011) TGF-beta regulates isoform switching of FGF receptors and epithelial-mesenchymal transition. EMBO J 30(4):783-95 |
| abstractText | The epithelial-mesenchymal transition (EMT) is a crucial event in wound healing, tissue repair, and cancer progression in adult tissues. Here, we demonstrate that transforming growth factor (TGF)-beta induced EMT and that long-term exposure to TGF-beta elicited the epithelial-myofibroblastic transition (EMyoT) by inactivating the MEK-Erk pathway. During the EMT process, TGF-beta induced isoform switching of fibroblast growth factor (FGF) receptors, causing the cells to become sensitive to FGF-2. Addition of FGF-2 to TGF-beta-treated cells perturbed EMyoT by reactivating the MEK-Erk pathway and subsequently enhanced EMT through the formation of MEK-Erk-dependent complexes of the transcription factor deltaEF1/ZEB1 with the transcriptional corepressor CtBP1. Consequently, normal epithelial cells that have undergone EMT as a result of combined TGF-beta and FGF-2 stimulation promoted the invasion of cancer cells. Thus, TGF-beta and FGF-2 may cooperate with each other and may regulate EMT of various kinds of cells in cancer microenvironment during cancer progression. |
