Novel signaling collaboration between TGF-β and adaptor protein Crk facilitates EMT in human lung cancer

Aiman Z. Elmansuri, Mishie A. Tanino, Roshan Mahabir, Lei Wang, Taichi Kimura, Hiroshi Nishihara, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Masumi Tsuda, Shinya Tanaka

研究成果: Article査読

18 被引用数 (Scopus)

抄録

The signaling adaptor protein Crk has been shown to play an important role in various human cancers. However, its regulatory machinery is not clear. Here, we demonstrated that Crk induced EMT in A549 human lung adenocarcinoma cells through differential regulation of Rac1/Snail and RhoA/Slug, leading to decreased expression of E-cadherin and increased N-cadherin, fibronectin, and MMP2 expression. Cancer cells with mesenchymal features produced TGF-β and also increased the levels of TGF-β receptor. TGF-β increased the endogenous levels of Crk and also augmented Crk-dependent expression of Snail and Slug, and conversely TGF-β receptor inhibitor suppressed the levels of Snail and Slug. Overexpression of Crk was observed at the invasive front of human lung cancer tissues and was significantly associated with poor prognosis. Thus, TGF-β and Crk collaborate to form a positive feedback loop to facilitate EMT, which may lead to the malignancy of human cancers possibly being affected by their microenvironment.

本文言語English
ページ(範囲)27094-27107
ページ数14
ジャーナルOncotarget
7
19
DOI
出版ステータスPublished - 2016 5月 10
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学

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