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(Journal Article) |
PloS one 9 (2): e89292 (2014)
Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
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
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.