RHBDL2 is a critical membrane protease for anoikis resistance in human malignant epithelial cells

Tsung Lin Cheng, Chao Han Lai, Shinn Jong Jiang, Jui Hsiang Hung, Shi Kai Liu, Bi Ing Chang, Guey Yueh Shi, Hua Lin Wu

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

Anoikis resistance allows metastatic tumor cells to survive in a homeless environment. Activation of epithelial growth factor receptor (EGFR) signaling is one of the key mechanisms for metastatic tumor cells to resist anoikis, yet the regulation mechanisms of homeless-triggered EGFR activation in metastatic tumor cells remain unclear. Rhomboid-like-2 (RHBDL2), an evolutionally conserved intramembrane serine protease, can cleave the EGF ligand and thus trigger EGFR activation. Herein, we demonstrated that RHBDL2 overexpression in human epithelial cells resulted in promotion of cell proliferation, reduction of cell adhesion, and suppression of anoikis. During long-term suspension cultures, increased RHBDL2 was only detected in aggressive tumor cell lines. Treatment with the rhomboid protease inhibitor or RHBDL2 shRNA increased cleaved caspase 3, a marker of apoptosis. Finally, inhibition of EGFR activation increased the cleaved caspase 3 and attenuated the detachment-induced focal adhesion kinase phosphorylation. Taken together, these findings provide evidence for the first time that RHBDL2 is a critical molecule in anoikis resistance of malignant epithelial cells, possibly through the EGFR-mediated signaling. Our study demonstrates RHBDL2 as a new therapeutic target for cancer metastasis.

原文English
文章編號902987
期刊Scientific World Journal
2014
DOIs
出版狀態Published - 2014

All Science Journal Classification (ASJC) codes

  • 生物化學、遺傳與分子生物學 (全部)
  • 環境科學 (全部)

指紋

深入研究「RHBDL2 is a critical membrane protease for anoikis resistance in human malignant epithelial cells」主題。共同形成了獨特的指紋。

引用此