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- Title
Store-Operated Ca<sup>2</sup><sup>+</sup> Entry (SOCE) Regulates Melanoma Proliferation and Cell Migration.
- Authors
Umemura, Masanari; Baljinnyam, Erdene; Feske, Stefan; De Lorenzo, Mariana S.; Xie, Lai-Hua; Feng, Xianfeng; Oda, Kayoko; Makino, Ayako; Fujita, Takayuki; Yokoyama, Utako; Iwatsubo, Mizuka; Chen, Suzie; Goydos, James S.; Ishikawa, Yoshihiro; Iwatsubo, Kousaku
- Abstract
Store-operated Ca2+ entry (SOCE) is a major mechanism of Ca2+ import from extracellular to intracellular space, involving detection of Ca2+ store depletion in endoplasmic reticulum (ER) by stromal interaction molecule (STIM) proteins, which then translocate to plasma membrane and activate Orai Ca2+ 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.
- Subjects
CELL migration; CELL proliferation; ENDOPLASMIC reticulum; CELL lines; CALMODULIN; CELL membranes
- Publication
PLoS ONE, 2014, Vol 9, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0089292