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

被引：192

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

页码：783 / 795

页数：13

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