Proteomic analysis reveals important role of 14-3-3 sigma in anoikis resistance of cholangiocarcinoma cells

作者：Khongmanee Amnart; Lirdprapamongkol Kriengsak; Tit oon Phanthakarn; Chokchaichamnankit Daranee; Svasti Jisnuson; Srisomsap Chantragan^*

来源：Proteomics, 2013, 13(21): 3157-3166.

DOI：10.1002/pmic.201300219

• 14-3-3 Sigma
• Anoikis resistance
• Cell biology
• Cholangiocarcinoma
• Metastasis

Cholangiocarcinoma (CCA), a high-prevalence cancer in Thailand, is highly metastatic and has high mortality rates. Anoikis resistance or the ability of cells to survive after detachment from extracellular matrix is a necessary property of metastatic cancer. Here, we report differential protein expression of an anoikis-resistant CCA cell line culture, under attachment conditions compared to nonattachment conditions, studied using 2DE coupled with protein identification by LC-MS/MS. Our data reveal the deregulation of proteins involved in stress response, cytoskeleton rearrangement, proapoptosis, cell proliferation, and glycolysis. Interestingly, 14-3-3 sigma (14-3-3 sigma) protein was intensely upregulated in detached CCA cells. Real-time RT-PCR analysis confirmed that only the sigma isotype was the most abundant transcript among 14-3-3 genes in CCA cells. Furthermore, silencing 14-3-3 sigma expression by small interfering RNA in CCA cells resulted in significantly increased percentage of cell death in detached culture. Our findings provide the first evidence showing that 14-3-3 sigma protein plays a crucial role in anoikis resistance of CCA cells. Therefore, 14-3-3 sigma might be a potential target in CCA therapy.

• 出版日期2013-11