PMID- 24586666 OWN - NLM STAT- MEDLINE DCOM- 20150113 LR - 20220316 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 2 DP - 2014 TI - Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. PG - e89292 LID - 10.1371/journal.pone.0089292 [doi] LID - e89292 AB - 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. FAU - Umemura, Masanari AU - Umemura M AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Baljinnyam, Erdene AU - Baljinnyam E AD - Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America. FAU - Feske, Stefan AU - Feske S AD - Department of Pathology, New York University School of Medicine, New York, New York, United States of America. FAU - De Lorenzo, Mariana S AU - De Lorenzo MS AD - Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America. FAU - Xie, Lai-Hua AU - Xie LH AD - Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America. FAU - Feng, Xianfeng AU - Feng X AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Oda, Kayoko AU - Oda K AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Makino, Ayako AU - Makino A AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Fujita, Takayuki AU - Fujita T AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Yokoyama, Utako AU - Yokoyama U AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Iwatsubo, Mizuka AU - Iwatsubo M AD - Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America. FAU - Chen, Suzie AU - Chen S AD - Department of Chemical Biology, Susan Lehman Cullen Laboratory of Cancer Research in the Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America. FAU - Goydos, James S AU - Goydos JS AD - Division of Surgical Oncology, Department of Surgery, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America. FAU - Ishikawa, Yoshihiro AU - Ishikawa Y AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan. FAU - Iwatsubo, Kousaku AU - Iwatsubo K AD - Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan ; Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America. LA - eng GR - R01 AI097302/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140221 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Calcium Channels) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Calcium Channels/metabolism MH - Calcium Signaling/*physiology MH - Cell Line, Tumor MH - Cell Movement/*physiology MH - Cell Proliferation/*physiology MH - Endoplasmic Reticulum/metabolism MH - Humans MH - Melanocytes/*metabolism MH - Melanoma/*metabolism/pathology MH - Mice MH - Skin Neoplasms/*metabolism/pathology PMC - PMC3931742 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/03/04 06:00 MHDA- 2015/01/15 06:00 PMCR- 2014/02/21 CRDT- 2014/03/04 06:00 PHST- 2013/05/29 00:00 [received] PHST- 2014/01/21 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2015/01/15 06:00 [medline] PHST- 2014/02/21 00:00 [pmc-release] AID - PONE-D-13-22172 [pii] AID - 10.1371/journal.pone.0089292 [doi] PST - epublish SO - PLoS One. 2014 Feb 21;9(2):e89292. doi: 10.1371/journal.pone.0089292. eCollection 2014.