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| Content Provider | PubMed Central |
|---|---|
| Author | Chen, Yih-fung Chiu, Wen-tai Chen, Ying-ting Lin, Pey-yun Huang, Huey-jy Chou, Cheng-yang Chang, Hsien-chang Tang, Ming-jer Shen, Meng-ru |
| Abstract | Store-operated Ca2+ entry (SOCE) is the principal Ca2+ entry mechanism in nonexcitable cells. Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca2+ sensor that triggers SOCE activation. However, the role of STIM1 in regulating cancer progression remains controversial and its clinical relevance is unclear. Here we show that STIM1-dependent signaling is important for cervical cancer cell proliferation, migration, and angiogenesis. STIM1 overexpression in tumor tissue is noted in 71% cases of early-stage cervical cancer. In tumor tissues, the level of STIM1 expression is significantly associated with the risk of metastasis and survival. EGF-stimulated cancer cell migration requires STIM1 expression and EGF increases the interaction between STIM1 and Orai1 in juxta-membrane areas, and thus induces Ca2+ influx. STIM1 involves the activation of Ca2+-regulated protease calpain, as well as Ca2+-regulated cytoplasmic kinase Pyk2, which regulate the focal-adhesion dynamics of migratory cervical cancer cells. Because of an increase of p21 protein levels and a decrease of Cdc25C protein levels, STIM1-silencing in cervical cancer cells significantly inhibits cell proliferation by arresting the cell cycle at the S and G2/M phases. STIM1 also regulates the production of VEGF in cervical cancer cells. Interference with STIM1 expression or blockade of SOCE activity inhibits tumor angiogenesis and growth in animal models, confirming the crucial role of STIM1-mediated Ca2+ influx in aggravating tumor development in vivo. These results make STIM1-dependent signaling an attractive target for therapeutic intervention. |
| Related Links | http://dx.doi.org/10.1073/pnas.1103315108 |
| Ending Page | 15230 |
| Page Count | 6 |
| Starting Page | 15225 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 37 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-09-13 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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