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

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 O...

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Main 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089292&type=printable
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author 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
author_facet 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
author_sort Masanari Umemura
collection DOAJ
description 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.
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spelling doaj-art-7a368dd04b7c4abb94f989a5d40c5cbc2025-08-20T02:15:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8929210.1371/journal.pone.0089292Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.Masanari UmemuraErdene BaljinnyamStefan FeskeMariana S De LorenzoLai-Hua XieXianfeng FengKayoko OdaAyako MakinoTakayuki FujitaUtako YokoyamaMizuka IwatsuboSuzie ChenJames S GoydosYoshihiro IshikawaKousaku IwatsuboStore-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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089292&type=printable
spellingShingle 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
Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
PLoS ONE
title Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
title_full Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
title_fullStr Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
title_full_unstemmed Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
title_short Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
title_sort store operated ca2 entry soce regulates melanoma proliferation and cell migration
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089292&type=printable
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