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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)27094-27107
Number of pages14
JournalOncotarget
Volume7
Issue number19
DOIs
Publication statusPublished - 2016 May 10
Externally publishedYes

Keywords

  • Crk
  • EMT
  • Lung cancer
  • Small G protein
  • TGF-β

ASJC Scopus subject areas

  • Oncology

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    Elmansuri, A. Z., Tanino, M. A., Mahabir, R., Wang, L., Kimura, T., Nishihara, H., Kinoshita, I., Dosaka-Akita, H., Tsuda, M., & Tanaka, S. (2016). Novel signaling collaboration between TGF-β and adaptor protein Crk facilitates EMT in human lung cancer. Oncotarget, 7(19), 27094-27107. https://doi.org/10.18632/oncotarget.8314