1. Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
- Author
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Umemura M, Baljinnyam E, Feske S, De Lorenzo MS, Xie LH, Feng X, Oda K, Makino A, Fujita T, Yokoyama U, Iwatsubo M, Chen S, Goydos JS, Ishikawa Y, and Iwatsubo K
- Subjects
- Animals, Calcium Channels metabolism, Cell Line, Tumor, Endoplasmic Reticulum metabolism, Humans, Melanoma pathology, Mice, Skin Neoplasms pathology, Calcium metabolism, Calcium Signaling physiology, Cell Movement physiology, Cell Proliferation physiology, Melanocytes metabolism, Melanoma metabolism, Skin Neoplasms metabolism
- Abstract
Store-operated Ca(2+) entry (SOCE) is a major mechanism of Ca(2) (+) import from extracellular to intracellular space, involving detection of Ca(2+) store depletion in endoplasmic reticulum (ER) by stromal interaction molecule (STIM) proteins, which then translocate to plasma membrane and activate Orai Ca(2+) channels there. We found that STIM1 and Orai1 isoforms were abundantly expressed in human melanoma tissues and multiple melanoma/melanocyte cell lines. We confirmed that these cell lines exhibited SOCE, which was inhibited by knockdown of STIM1 or Orai1, or by a pharmacological SOCE inhibitor. Inhibition of SOCE suppressed melanoma cell proliferation and migration/metastasis. Induction of SOCE was associated with activation of extracellular-signal-regulated kinase (ERK), and was inhibited by inhibitors of calmodulin kinase II (CaMKII) or Raf-1, suggesting that SOCE-mediated cellular functions are controlled via the CaMKII/Raf-1/ERK signaling pathway. Our findings indicate that SOCE contributes to melanoma progression, and therefore may be a new potential target for treatment of melanoma, irrespective of whether or not Braf mutation is present.
- Published
- 2014
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