Referenced in: none

Automatically associated channels: Slo1

Title: Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.

Authors: Masanari Umemura, Erdene Baljinnyam, Stefan Feske, Mariana S De Lorenzo, Lai-Hua Xie, Xianfeng Feng, Kayoko Oda, Ayako Makino, Takayuki Fujita, Utako Yokoyama, Mizuka Iwatsubo, Suzie Chen, James S Goydos, Yoshihiro Ishikawa, Kousaku Iwatsubo

Journal, date & volume: PLoS ONE, 2014 , 9, e89292

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24586666

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.