PMID- 30544747 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200225 IS - 2073-4409 (Print) IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 7 IP - 12 DP - 2018 Dec 10 TI - Silencing Heat Shock Protein 27 Inhibits the Progression and Metastasis of Colorectal Cancer (CRC) by Maintaining the Stability of Stromal Interaction Molecule 1 (STIM1) Proteins. LID - 10.3390/cells7120262 [doi] LID - 262 AB - The incidence of colorectal cancer (CRC) has significantly increased in recent decades, and this disease has become an important health issue worldwide. Currently, there is no useful prognostic or diagnostic biomarker for CRC. Heat shock protein 27 (HSP27) is a chaperone that interacts with many proteins. HSP27 has been shown to be overexpressed in many cancers, including colon cancer, and its overexpression is related to poor disease outcome. Although the importance of HSP27 as a biomarker cannot be underrated, its detailed mechanisms in colon cancer are still unclear. In vitro studies have indicated that silencing HSP27 reduces the proliferation, migration and invasion of colon cancer cells, and xenograft models have shown that silencing HSP27 decreases tumor progression. Tissue array results showed that colon cancer patients with high expression of HSP27 exhibited poor prognosis. In addition, we found a reduction of calcium influx through a decrease in STIM1 protein after HSP27 was abolished. The formation of puncta was decreased in HSP27 knockdown (HSP27KD) cells after thapsigargin (TG) treatment. Finally, we confirmed that the reduction of STIM1 after HSP27 silencing may be due to a loss of STIM1 stability instead of transcription. HSP27 may interact with STIM1 but not Orai1, as shown by immunoprecipitation assays. HSP27 and STIM1 were co-expressed in CRC specimens. Our study showed that HSP27 is a key mediator in the progression and metastasis of CRC by regulating the store-operated calcium entry. This novel pathway may provide a new direction for development of therapeutic strategies for CRC. FAU - Huang, Chien-Yu AU - Huang CY AD - Department of Surgery, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. cyh@tmu.edu.tw. AD - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei 110, Taiwan. cyh@tmu.edu.tw. FAU - Wei, Po-Li AU - Wei PL AD - Department of Surgery, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. poliwei@tmu.edu.tw. AD - Division of Colorectal Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan. poliwei@tmu.edu.tw. AD - Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan. poliwei@tmu.edu.tw. AD - Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan. poliwei@tmu.edu.tw. AD - Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei 110, Taiwan. poliwei@tmu.edu.tw. FAU - Chen, Wei-Yu AU - Chen WY AD - Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. wychen.patho@gmail.com. AD - Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan. wychen.patho@gmail.com. FAU - Chang, Wei-Chiao AU - Chang WC AD - School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. weichiao.chang@gmail.com. AD - Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, Taipei Medical University, Taipei 110, Taiwan. weichiao.chang@gmail.com. FAU - Chang, Yu-Jia AU - Chang YJ AUID- ORCID: 0000-0003-3978-3244 AD - Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan. r5424012@tmu.edu.tw. AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. r5424012@tmu.edu.tw. LA - eng PT - Journal Article DEP - 20181210 PL - Switzerland TA - Cells JT - Cells JID - 101600052 PMC - PMC6315635 OTO - NOTNLM OT - CRC OT - ER OT - HSP27 OT - SOCE OT - STIM1 COIS- The authors have no conflict of interest in this study. EDAT- 2018/12/14 06:00 MHDA- 2018/12/14 06:01 PMCR- 2018/12/01 CRDT- 2018/12/15 06:00 PHST- 2018/11/13 00:00 [received] PHST- 2018/12/02 00:00 [revised] PHST- 2018/12/07 00:00 [accepted] PHST- 2018/12/15 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2018/12/14 06:01 [medline] PHST- 2018/12/01 00:00 [pmc-release] AID - cells7120262 [pii] AID - cells-07-00262 [pii] AID - 10.3390/cells7120262 [doi] PST - epublish SO - Cells. 2018 Dec 10;7(12):262. doi: 10.3390/cells7120262.