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

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Store-operated Ca2+ entry (SOCE) is a major mechanism of Ca 2+ 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.

Original languageEnglish (US)
Article numbere89292
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 21 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Umemura, M., Baljinnyam, E., Feske, S., De Lorenzo, M. S., Xie, L. H., Feng, X., Oda, K., Makino, A., Fujita, T., Yokoyama, U., Iwatsubo, M., Chen, S., Goydos, J. S., Ishikawa, Y., & Iwatsubo, K. (2014). Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. PloS one, 9(2), [e89292]. https://doi.org/10.1371/journal.pone.0089292