Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/28677
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    標題: RHBDL2 Is a Critical Membrane Protease for Anoikis Resistance in Human Malignant Epithelial Cells
    作者: Cheng, Tsung-Lin
    Lai, Chao-Han
    Jiang, Shinn-Jong
    Hung, Jui-Hsiang
    Liu, Shi-Kai
    Chang, Bi-Ing
    Shi, Guey-Yueh
    Wu, Hua-Lin
    貢獻者: 生物科技系
    關鍵字: RHOMBOID PROTEASE
    CANCER-CELLS
    APOPTOSIS
    DROSOPHILA
    ACTIVATION
    THROMBOMODULIN
    INTEGRINS
    ADHESION
    MATRIX
    GENE
    日期: 2014
    上傳時間: 2015-05-06 21:24:49 (UTC+8)
    出版者: Hindawi Publishing Corporation
    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.
    關聯: Scientific World Journal, 90287
    顯示於類別:[生物科技系(所)] 期刊論文

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