title: Suppression of STIM1 inhibits human glioblastoma cell proliferation and induces G0/G1 phase arrest.
abstract: BACKGROUND
  Depletion of calcium (Ca2+) from the endoplasmic reticulum (ER) activates the ubiquitous store-operated Ca2+ entry (SOCE) pathway which sustains long-term Ca2+ signals and is critical for cellular functions. Stromal interacting molecule 1 (STIM1) serves a dual role as an ER Ca2+ sensor and activator of SOCE. Aberrant expression of STIM1 could be observed in several human cancer cells. However, the role of STIM1 in regulating tumorigenesis of human glioblastoma still remains unclear.
  
  
  METHODS
  Expression of STIM1 protein in a panel of human glioblastoma cell lines (U251, U87 and U373) in different transformation level were evaluated by Western blot method. STIM1 loss of function was performed on U251 cells, derived from grade IV astrocytomas-glioblastoma multiforme with a lentvirus-mediated short harpin RNA (shRNA) method. The biological impacts after knock down of STIM1 on glioblastoma cells were investigated in vitro and in vivo.
  
  
  RESULTS
  We discovered that STIM1 protein was expressed in U251, U87 and U373 cells, and especially higher in U251 cells. RNA interference efficiently downregulated the expression of STIM1 in U251 cells at both mRNA and protein levels. Specific downregulation of STIM1 inhibited U251 cell proliferation by inducing cell cycle arrest in G0/G1 phase through regulation of cell cycle-related genes, such as p21Waf1/Cip1, cyclin D1 and cyclin-dependent kinase 4 (CDK4), and the antiproliferative effect of STIM1 silencing was also observed in U251 glioma xenograft tumor model.
  
  
  CONCLUSIONS
  Our findings confirm STIM1 as a rational therapeutic target in human glioblastoma, and also indicate that lentivirus-mediated STIM1 silencing is a promising therapeutic strategy for human glioblastoma.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing 100730, PR China.
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Junji
authors.initials: J
authors.lastname: Wei
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000502:physiology; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D000071737:Stromal Interaction Molecule 1; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1