TY - JOUR
T1 - Store-Operated Ca2+ entry in tumor progression
T2 - From molecular mechanisms to clinical implications
AU - Chen, Yih Fung
AU - Lin, Peng Chan
AU - Yeh, Yu Min
AU - Chen, Li Hsien
AU - Shen, Meng Ru
N1 - Funding Information:
This research was funded by the Ministry of Science and Technology (MOST 106-2319-B-006-001-, 108-2634-F-006-011-, and 108-2319-B-006-001-), the Ministry of Health and Welfare (MOHW106-TDU-B-211-113003, MOHW108-TDU-B-211-124018), the National Health Research Institutes (NHRI-108A1-CACO-02181811), National Cheng Kung University Hospital, and the Kaohsiung Medical University Research Foundation (KMUM108010), Taiwan.
Publisher Copyright:
© 2019 by the authors.
PY - 2019/7
Y1 - 2019/7
N2 - The remodeling of Ca2+ homeostasis has been implicated as a critical event in driving malignant phenotypes, such as tumor cell proliferation, motility, and metastasis. Store-operated Ca2+ entry (SOCE) that is elicited by the depletion of the endoplasmic reticulum (ER) Ca2+ stores constitutes the major Ca2+ influx pathways in most nonexcitable cells. Functional coupling between the plasma membrane Orai channels and ER Ca2+-sensing STIM proteins regulates SOCE activation. Previous studies in the human breast, cervical, and other cancer types have shown the functional significance of STIM/Orai-dependent Ca2+ signals in cancer development and progression. This article reviews the information on the regulatory mechanisms of STIM- and Orai-dependent SOCE pathways in the malignant characteristics of cancer, such as proliferation, resistance, migration, invasion, and metastasis. The recent investigations focusing on the emerging importance of SOCE in the cells of the tumor microenvironment, such as tumor angiogenesis and antitumor immunity, are also reviewed. The clinical implications as cancer therapeutics are discussed.
AB - The remodeling of Ca2+ homeostasis has been implicated as a critical event in driving malignant phenotypes, such as tumor cell proliferation, motility, and metastasis. Store-operated Ca2+ entry (SOCE) that is elicited by the depletion of the endoplasmic reticulum (ER) Ca2+ stores constitutes the major Ca2+ influx pathways in most nonexcitable cells. Functional coupling between the plasma membrane Orai channels and ER Ca2+-sensing STIM proteins regulates SOCE activation. Previous studies in the human breast, cervical, and other cancer types have shown the functional significance of STIM/Orai-dependent Ca2+ signals in cancer development and progression. This article reviews the information on the regulatory mechanisms of STIM- and Orai-dependent SOCE pathways in the malignant characteristics of cancer, such as proliferation, resistance, migration, invasion, and metastasis. The recent investigations focusing on the emerging importance of SOCE in the cells of the tumor microenvironment, such as tumor angiogenesis and antitumor immunity, are also reviewed. The clinical implications as cancer therapeutics are discussed.
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U2 - 10.3390/cancers11070899
DO - 10.3390/cancers11070899
M3 - Review article
AN - SCOPUS:85068646457
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 7
M1 - 899
ER -