title: Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
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.
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Umemura
authors.affiliation: 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.
authors.forename: Erdene
authors.initials: E
authors.lastname: Baljinnyam
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
authors.affiliation: 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.
authors.forename: Mariana S
authors.initials: MS
authors.lastname: De Lorenzo
authors.affiliation: 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.
authors.forename: Lai-Hua
authors.initials: LH
authors.lastname: Xie
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Feng
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Oda
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Makino
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Utako
authors.initials: U
authors.lastname: Yokoyama
authors.affiliation: 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.
authors.forename: Mizuka
authors.initials: M
authors.lastname: Iwatsubo
authors.affiliation: 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.
authors.forename: Suzie
authors.initials: S
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: James S
authors.initials: JS
authors.lastname: Goydos
authors.affiliation: Cardiovascular Research Institute, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: 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.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Iwatsubo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D015220:Calcium Channels; D002118:Calcium