Store-Operated Ca2+ Entry in Tumor Progression: From Molecular Mechanisms to Clinical Implications

Store-Operated Ca2+ Entry in Tumor Progression: From Molecular Mechanisms to Clinical Implications

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 maj...

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Bibliographic Details
Published in:Cancers 2019-06, Vol.11 (7), p.899
Main Authors: Chen, Yih-Fung, Lin, Peng-Chan, Yeh, Yu-Min, Chen, Li-Hsien, Shen, Meng-Ru
Format: Article
Language:eng
Subjects:
Angiogenesis
Breast cancer
Ca2+ signaling
Calcium (reticular)
Calcium channels
Calcium homeostasis
Calcium influx
Calcium signalling
Cell proliferation
Cervical cancer
Cervix
Endoplasmic reticulum
Homeostasis
Lymphatic system
Medical prognosis
Metastases
Metastasis
migration
Molecular modelling
Multiple myeloma
orai
Phenotypes
Prostate cancer
Proteins
Review
Sensors
store-operated Ca2+ entry (SOCE)
stromal interaction molecule (STIM)
Tumor microenvironment
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694