Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth. Issue 11 (25th January 2022)

• Record Type: Journal Article
• Authors: Xie, Jiansheng; Ma, Guolin; Zhou, Lijuan; He, Lian; Zhang, Zhao; Tan, Peng; Huang, Zixian; Fang, Shaohai; Wang, Tianlu; Lee, Yi‐Tsang; Wen, Shufan; Siwko, Stefan; Wang, Liuqing; Liu, Jindou; Du, Yangchun; Zhang, Ningxia; Liu, Xiaoxuan; Han, Leng; Huang, Yun; Wang, Rui; Wang, Youjun; Zhou, Yubin; Han, Weidong
• Is Part Of: Advanced science. Volume 9:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-25
• Subjects: calcium signaling -- cell signaling -- glioblastoma -- splicing -- STIM1; Science -- Periodicals; 505
• DOI: 10.1002/advs.202103940
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Deregulated store‐operated calcium entry (SOCE) mediated by aberrant STIM1‐ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1β, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1β, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca 2+ signaling. At the molecular level, the 31‐residue insertion destabilizes STIM1β by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1β depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant‐specific tumor‐promoting role of STIM1β that can be potentially targeted for glioblastoma intervention. Abstract : The authors report a novel splice variant of stromal interaction molecule 1, designated STIM1β, that is abnormally upregulated in glioma cells. A 31‐residue insertion in the cytosolic domain of STIM1β renders itself prone for activation, thereby perturbing Ca 2+ homeostasis and promoting glioblastoma growth. Their study establishes a splicing variant‐specific tumor‐promoting role of STIM1β that can be targeted for cancer intervention.