Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth
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 en...
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202103940 |
| _version_ | 1811335190129147904 |
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| author | Jiansheng Xie Guolin Ma Lijuan Zhou Lian He Zhao Zhang Peng Tan Zixian Huang Shaohai Fang Tianlu Wang Yi‐Tsang Lee Shufan Wen Stefan Siwko Liuqing Wang Jindou Liu Yangchun Du Ningxia Zhang Xiaoxuan Liu Leng Han Yun Huang Rui Wang Youjun Wang Yubin Zhou Weidong Han |
| author_facet | Jiansheng Xie Guolin Ma Lijuan Zhou Lian He Zhao Zhang Peng Tan Zixian Huang Shaohai Fang Tianlu Wang Yi‐Tsang Lee Shufan Wen Stefan Siwko Liuqing Wang Jindou Liu Yangchun Du Ningxia Zhang Xiaoxuan Liu Leng Han Yun Huang Rui Wang Youjun Wang Yubin Zhou Weidong Han |
| author_sort | Jiansheng Xie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:20:29Z |
| format | Article |
| id | doaj.art-733b58bf5ebb41d489d9290c72d77544 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-13T17:20:29Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-733b58bf5ebb41d489d9290c72d775442022-12-22T02:38:00ZengWileyAdvanced Science2198-38442022-04-01911n/an/a10.1002/advs.202103940Identification of a STIM1 Splicing Variant that Promotes Glioblastoma GrowthJiansheng Xie0Guolin Ma1Lijuan Zhou2Lian He3Zhao Zhang4Peng Tan5Zixian Huang6Shaohai Fang7Tianlu Wang8Yi‐Tsang Lee9Shufan Wen10Stefan Siwko11Liuqing Wang12Jindou Liu13Yangchun Du14Ningxia Zhang15Xiaoxuan Liu16Leng Han17Yun Huang18Rui Wang19Youjun Wang20Yubin Zhou21Weidong Han22Department 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. ChinaCenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USABeijing Key Laboratory of Gene Resource and Molecular Development College of Life Sciences Beijing Normal University Beijing 100875 P. R. ChinaCenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USAMOE Key Laboratory of Metabolism and Molecular Medicine Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Fudan University Shanghai ChinaCenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Epigenetics and Disease Prevention Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USABeijing Key Laboratory of Gene Resource and Molecular Development College of Life Sciences Beijing Normal University Beijing 100875 P. R. ChinaBeijing Key Laboratory of Gene Resource and Molecular Development College of Life Sciences Beijing Normal University Beijing 100875 P. R. ChinaBeijing Key Laboratory of Gene Resource and Molecular Development College of Life Sciences Beijing Normal University Beijing 100875 P. R. ChinaDepartment 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. ChinaCenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USADepartment of Biochemistry and Molecular Biology University of Texas Health Science Center at Houston McGovern Medical School Houston TX 77030 USACenter for Epigenetics and Disease Prevention Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USACenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USABeijing Key Laboratory of Gene Resource and Molecular Development College of Life Sciences Beijing Normal University Beijing 100875 P. R. ChinaCenter for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USADepartment 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. ChinaAbstract 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.https://doi.org/10.1002/advs.202103940calcium signalingcell signalingglioblastomasplicingSTIM1 |
| spellingShingle | Jiansheng Xie Guolin Ma Lijuan Zhou Lian He Zhao Zhang Peng Tan Zixian Huang Shaohai Fang Tianlu Wang Yi‐Tsang Lee Shufan Wen Stefan Siwko Liuqing Wang Jindou Liu Yangchun Du Ningxia Zhang Xiaoxuan Liu Leng Han Yun Huang Rui Wang Youjun Wang Yubin Zhou Weidong Han Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth Advanced Science calcium signaling cell signaling glioblastoma splicing STIM1 |
| title | Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth |
| title_full | Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth |
| title_fullStr | Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth |
| title_full_unstemmed | Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth |
| title_short | Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth |
| title_sort | identification of a stim1 splicing variant that promotes glioblastoma growth |
| topic | calcium signaling cell signaling glioblastoma splicing STIM1 |
| url | https://doi.org/10.1002/advs.202103940 |
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