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

作者：Elmansuri Aiman Z; Tanino Mishie A^*; Mahabir Roshan; Wang Lei; Kimura Taichi; Nishihara Hiroshi; Kinoshita Ichiro; Dosaka Akita Hirotoshi; Tsuda Masumi; Tanaka Shinya^*

来源：Oncotarget, 2016, 7(19): 27094-27107.

DOI：10.18632/oncotarget.8314

• Crk
• EMT
• lung cancer
• small G protein
• TGF-beta

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-beta and also increased the levels of TGF-beta receptor. TGF-beta increased the endogenous levels of Crk and also augmented Crk-dependent expression of Snail and Slug, and conversely TGF-beta 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-beta 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.

• 出版日期2016-5-10