Blockade of store-operated Ca²⁺ entry inhibits hepatocarcinoma cell migration and invasion by regulating focal adhesion turnover

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• 作者：Ning Yang^a ; ¹ ; Ying Tang^b ; ¹ ; Fang Wang^c ; Haibin Zhang^a ; Dan Xu^c ; Yafeng Shen^b ; Shuhan Sun^c ; Guangshun Yang^a ; ^{lancet829@gmail.com}
• 关键词：Store-operated Ca2+ entry ; STIM1 ; Hepatocellular carcinoma ; Focal adhesion turnover ; Focal adhesion kinase
• 刊名：Cancer Letters
• 出版年：2013
• 出版时间：28 April, 2013
• 年：2013
• 卷：330
• 期：2
• 页码：163-169
• 全文大小：928 K

文摘

Store-operated Ca²⁺ entry (SOCE) is a main Ca²⁺ influx pathway controlling the intracellular Ca²⁺ concentration in normal hepatocytes and hepatocellular carcinoma (HCC) cells. Ca²⁺ influx has been demonstrated to be involved in liver oncogenesis. Stromal interacting molecule (STIM) 1 acts as a sensor for the level of Ca²⁺ stored in the endoplasmic reticulum, and Orai1 protein constitutes the pore-forming subunit of the store-operated channels. Recently, STIM1 and Orai1 were found critical for breast tumor cell migration and metastasis. However, the effects of Ca²⁺ influx pathway on migration and metastasis have not been studied in hepatocellular carcinoma. Here, we found that STIM1 had a higher expression in hepatoma tissues than in precancerous tissues of the same patients. In general, STIM expression is elevated in HCC cell lines compared to a normal hepatocyte cell line. HCC-LM3 cell, which has a higher migration ability, expresses five times higher level of STIM than other HCC cell lines. STIM1 could then be explored as a prognostic marker to screen liver cancer patients with high metastatic potential. Inhibition of SOCE and STIM1 enhance focal adhesions and decrease the focal adhesion turnover, suggesting the therapeutic potential of SOCE and STIM1 as new molecular targets for metastatic HCC.