TGF-β regulates isoform switching of FGF receptors and epithelial-mesenchymal transition

被引：196
作者：
Shirakihara, Takuya [2 ]
Horiguchi, Kana
Miyazawa, Keiji [3 ]
Ehata, Shogo
Shibata, Tatsuhiro [2 ]
Morita, Ikuo [4 ,5 ]
Miyazono, Kohei [1 ]
Saitoh, Masao [3 ,4 ,5 ]
机构：
[1] Univ Tokyo, Dept Mol Pathol, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan
[2] Natl Canc Ctr, Div Canc Genom, Tokyo, Japan
[3] Univ Yamanashi, Dept Biochem, Interdisciplinary Grad Sch Med Engn, Yamanashi 4093899, Japan
[4] Tokyo Med & Dent Univ, Grad Sch, Dept Cellular Physiol Chem, Tokyo, Japan
[5] Tokyo Med & Dent Univ, Grad Sch, Global Ctr Excellence GCOE Program, Int Res Ctr Mol Sci Tooth & Bone, Tokyo, Japan
来源：
EMBO JOURNAL | 2011年 / 30卷 / 04期
关键词：
EMT; FGF-2; FGF receptor; TGF-beta; dEF1; PROSTATE ADENOCARCINOMA; TUMOR-GROWTH; CELLS; PHOSPHORYLATION; IDENTIFICATION; COREPRESSORS; FIBROBLASTS; SUPPRESSION; PROGRESSION; INDUCTION;
D O I：
10.1038/emboj.2010.351
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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-b 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 delta EF1/ZEB1 with the transcriptional corepressor CtBP1. Consequently, normal epithelial cells that have undergone EMT as a result of combined TGF-b and FGF-2 stimulation promoted the invasion of cancer cells. Thus, TGF-b and FGF-2 may cooperate with each other and may regulate EMT of various kinds of cells in cancer microenvironment during cancer progression. The EMBO Journal (2011) 30, 783-795. doi:10.1038/emboj.2010.351; Published online 11 January 2011
引用
收藏
页码：783 / 795
页数：13
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