PMID- 28494008 OWN - NLM STAT- MEDLINE DCOM- 20170913 LR - 20190221 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 5 DP - 2017 TI - Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma. PG - e0177484 LID - 10.1371/journal.pone.0177484 [doi] LID - e0177484 AB - Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study. FAU - Li, Ping AU - Li P AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. FAU - Bian, Xue-Yan AU - Bian XY AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. AD - Cardiopulmonary Function Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. FAU - Chen, Qing AU - Chen Q AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. AD - Cardiopulmonary Function Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. FAU - Yao, Xiao-Feng AU - Yao XF AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. FAU - Wang, Xu-Dong AU - Wang XD AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. FAU - Zhang, Wen-Chao AU - Zhang WC AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. FAU - Tao, Ying-Jie AU - Tao YJ AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. FAU - Jin, Rui AU - Jin R AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. FAU - Zhang, Lun AU - Zhang L AUID- ORCID: 0000-0002-3945-9463 AD - Departments of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, the People's Republic of China. AD - National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, the People's Republic of China. LA - eng PT - Journal Article DEP - 20170511 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antineoplastic Agents) RN - 0 (Stromal Interaction Molecule 1) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects/*genetics MH - Blotting, Western MH - Carcinoma, Squamous Cell/genetics/*physiopathology MH - Cell Cycle/genetics MH - Cell Line, Tumor MH - Cell Proliferation/drug effects/genetics MH - Endoplasmic Reticulum Stress/drug effects MH - Gene Expression Regulation, Neoplastic/drug effects/genetics MH - Head and Neck Neoplasms/genetics/*physiopathology MH - Humans MH - Mice MH - Mice, Nude MH - Real-Time Polymerase Chain Reaction MH - Squamous Cell Carcinoma of Head and Neck MH - Stromal Interaction Molecule 1/*genetics/metabolism MH - Thapsigargin/pharmacology MH - Xenograft Model Antitumor Assays PMC - PMC5426681 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/05/12 06:00 MHDA- 2017/09/14 06:00 PMCR- 2017/05/11 CRDT- 2017/05/12 06:00 PHST- 2017/01/19 00:00 [received] PHST- 2017/04/27 00:00 [accepted] PHST- 2017/05/12 06:00 [entrez] PHST- 2017/05/12 06:00 [pubmed] PHST- 2017/09/14 06:00 [medline] PHST- 2017/05/11 00:00 [pmc-release] AID - PONE-D-17-02459 [pii] AID - 10.1371/journal.pone.0177484 [doi] PST - epublish SO - PLoS One. 2017 May 11;12(5):e0177484. doi: 10.1371/journal.pone.0177484. eCollection 2017.