title: Blockade of store-operated Ca(2+) entry inhibits hepatocarcinoma cell migration and invasion by regulating focal adhesion turnover.
abstract: Store-operated Ca(2+) entry (SOCE) is a main Ca(2+) influx pathway controlling the intracellular Ca(2+) concentration in normal hepatocytes and hepatocellular carcinoma (HCC) cells. Ca(2+) influx has been demonstrated to be involved in liver oncogenesis. Stromal interacting molecule (STIM) 1 acts as a sensor for the level of Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Hepatic Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Shen
authors.forename: Shuhan
authors.initials: S
authors.lastname: Sun
authors.forename: Guangshun
authors.initials: G
authors.lastname: Yang
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium