The distinct role of STIM1 and STIM2 in the regulation of store‐operated Ca2+ entry and cellular function

Stromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum (ER) Ca2+ sensors that initiate store‐operated Ca 2+ entry (SOCE). The roles of STIM1‐mediated SOCE in cancer biology have been highlighted in different types of cancer, but that of STIM2 is unknown. By the model of cervical can...

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Published in:Journal of cellular physiology 2019-06, Vol.234 (6), p.8727-8739
Main Authors: Chen, Yih‐Fung, Chen, Li‐Hsien, Shen, Meng‐Ru
Format: Article
Language:English
Subjects:
Calcium (reticular)
Calcium channels
Calcium influx
Calcium ions
Cancer
Cell adhesion & migration
Cell migration
Cell proliferation
Cervical cancer
Cervix
EB1
Endoplasmic reticulum
Human papillomavirus
Invasiveness
Microtubules
Orai1
Orai1 protein
Proteins
STIM1 protein
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Summary:Stromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum (ER) Ca2+ sensors that initiate store‐operated Ca 2+ entry (SOCE). The roles of STIM1‐mediated SOCE in cancer biology have been highlighted in different types of cancer, but that of STIM2 is unknown. By the model of cervical cancer, here we focus on the cooperative regulation of SOCE by STIM proteins and their distinct roles in cellular function. Immunofluorescent stainings of surgical specimens of cervical cancer show that STIM1 and STIM2 are abundant in tumor tissues, but STIM1 is the major ER Ca 2+ sensor identified in the invasive front of cancer tissues. STIM1 or STIM2 overexpression in cervical cancer SiHa cells induces an upregulated SOCE. Regarding cellular function, STIM1 and STIM2 are necessary for cell proliferation, whereas STIM1 is the dominant ER Ca 2+ sensor involved in cell migration. During SOCE, STIM1 is aggregated and translocated towards the Orai1‐containing plasma membrane in association with the microtubule plus‐end binding protein EB1. In contrast, STIM2 is constitutively aggregated without significant trafficking or association with microtubules. These results show the distinct role of STIM1 and STIM2 in SOCE and cellular function of cervical cancer cells. Although the roles of STIM1 in cancer cells have been well studied, the role of STIM2 in cellular function remains unclear. By the model of cervical cancer, here we demonstrate the distinct role of STIM1 and STIM2 in the regulation of store‐operated Ca2+ entry (SOCE) and cellular function. The results show that both STIM1 and STIM2 are necessary for cancer cell proliferation, whereas STIM1 is the dominant endoplasmic reticulum (ER) Ca 2+ sensor involved in cancer cell migration. EGF: epidermal growth factor; SOC: store‐operated Ca 2+
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.27532