STIM1 expression is associated with osteosarcoma cell survival

Jie Zang; Dongqing Zuo; Kristen L Shogren; Carl T Gustafson; Zifei Zhou; Michael A Thompson; Ruiwei Guo; Y S Prakash; Lichun Lu; Wei Guo; Avudaiappan Maran; Michael J Yaszemski

doi:10.21147/j.issn.1000-9604.2019.01.15

STIM1 expression is associated with osteosarcoma cell survival

Chin J Cancer Res. 2019 Feb;31(1):203-211. doi: 10.21147/j.issn.1000-9604.2019.01.15.

Authors

Jie Zang^{1

2}, Dongqing Zuo^{1

3}, Kristen L Shogren¹, Carl T Gustafson¹, Zifei Zhou¹, Michael A Thompson⁴, Ruiwei Guo⁵, Y S Prakash^{3

6}, Lichun Lu^{1

6}, Wei Guo², Avudaiappan Maran^{1

6}, Michael J Yaszemski^{1

6}

Affiliations

¹ Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
² Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China.
³ Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
⁴ Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
⁵ Department of Cardiology, Kunming General Hospital of Chengdu Military Command of PLA, Kunming 650032, China.
⁶ Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.

PMID: 30996578
PMCID: PMC6433589
DOI: 10.21147/j.issn.1000-9604.2019.01.15

Abstract

Objective: To examine the role of store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca²⁺ contributes to the regulation of osteosarcoma cells.

Methods: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) activity by luciferase assays.

Results: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca²⁺ channels involved down-regulation of NFATc1 in osteosarcoma cells.

Conclusions: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca²⁺ entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.

Keywords: Calcium; NFATc1; SOCE; STIM1; osteosarcoma.