Related Experiment Video
Updated: Oct 5, 2025
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth
Jiansheng Xie1, Guolin Ma2, Lijuan Zhou3
1Department of Medical Oncology, Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China.
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 Ca2+ 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.
Insights
A newly identified STIM1β protein variant promotes glioma growth by enhancing calcium signaling. Targeting this STIM1β splicing variant may offer new glioblastoma treatment strategies.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Aberrant store-operated calcium entry (SOCE) via STIM1-ORAI1 signaling is linked to cancer.
- Understanding the molecular mechanisms of SOCE dysregulation is crucial for cancer therapy.
Purpose of the Study:
- To identify and characterize novel STIM1 splicing variants involved in cancer.
- To investigate the role of STIM1β in glioma development and progression.
Main Methods:
- Identification of STIM1β alternative splicing variant.
- Analysis of STIM1β expression in glioma tissues.
- Molecular studies on STIM1β function in calcium signaling and cell proliferation.
- In vitro and in vivo experiments to assess tumor growth.
Main Results:
- A novel STIM1 splicing variant, STIM1β, with an extra exon encoding 31 amino acids was identified.
- STIM1β is upregulated in glioma tissues and enhances SOCE by accelerating STIM1 activation.
- STIM1β depletion inhibits glioblastoma cell proliferation and tumor growth in vitro and in vivo.
Conclusions:
- STIM1β exhibits a splicing variant-specific tumor-promoting role in glioblastoma.
- STIM1β represents a potential therapeutic target for glioblastoma intervention.
More Related Videos
10:28Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
Published on: January 10, 2018
12:52Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
