Fyn mediates transforming growth factor-beta1-induced down-regulation of E-cadherin in human A549 lung cancer cells

• Published in: Biochemical and biophysical research communications Vol. 407; no. 1; pp. 181 - 184
• Main Authors: Kim, An Na, Jeon, Woo-Kwang, Lim, Kyu-Hyoung, Lee, Hui-Young, Kim, Woo Jin, Kim, Byung-Chul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2011
• Subjects: Cadherins - antagonists & inhibitors; Cadherins - metabolism; Cell Line, Tumor; Down-Regulation; E-cadherin; Fyn; Humans; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Proto-Oncogene Proteins c-fyn - genetics; Proto-Oncogene Proteins c-fyn - metabolism; RNA, Small Interfering - genetics; Snail; Snail Family Transcription Factors; TGF-beta1; Transcription Factors - metabolism; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta1 - pharmacology; Fyn; p38; Snail; TGF-beta1; E-cadherin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.02.134

► Fyn is involved in the down-regulation of E-cadherin by TGF-β1. ► p38 Kinase is required for TGF-β1-induced suppression of E-cadherin. ► Snail is involved in the repression of TGF-β1-mediated E-cadherin expression as a downstream target of Fyn-p38-linked signaling. Transforming growth factor-beta (TGF-β) signaling positively contributes to the regulation of tumor metastasis. However, the underlying molecular mechanisms are less well defined. We here show that Fyn, a member of Src family tyrosine kinases, plays a critical role in mediating TGF-β1-induced down-regulation of E-cadherin in human A549 lung cancer cells. Blockade of Fyn with siRNA knockdown or ligand-binding defective mutant significantly lowered the ability of TGF-β1 to repress E-cadherin expression. Furthermore, our results demonstrated that Fyn facilitates TGF-β1-mediated suppression of E-cadherin through p38 kinase-dependent induction of Snail. Collectively, our findings identify a Fyn-p38-Snail cascade as a new signaling pathway mediating oncogenic TGF-β function.