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SH3GL3 acts as a novel tumor suppressor in glioblastoma tumorigenesis by inhibiting STAT3 signaling.

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机构: [a]Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China [b]Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China [c]Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China [d]Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China
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关键词: Glioblastoma SH3GL3 Glioma stem cell Tumor suppressor STAT3 Therapeutic target

摘要:
Glioblastoma (GBM) is the most severe malignant tumors of the central nervous system. Glioblastoma stem cells (GSCs) are considered to account for tumor initiation, therapeutic resistance, and tumor relapse. Yet the underlying mechanisms of GSC stemness maintenance remain largely unknown. Abnormal activation of STAT3 signaling is required for GBM tumorigenesis and GSC self-renewal. In this study, we provide evidence that SH3GL3 was weakly expressed in GBM and its high expression correlated with a favorable prognosis for GBM patients. Ectopic of SH3GL3 expression considerably inhibits GBM cell malignant behaviors, including GBM cell proliferation, migration as well as GSCs self-renewal ability. Mechanistically, we first found that SH3GL3 interacts with STAT3, which thereby inhibiting STAT3 nuclear localization. Overexpression of constitutively activated (STAT3-C) restored the growth, migration and self-renewal ability impaired by overexpression of SH3GL3. Together, our work shed insight on a critical regulatory mechanism mediated by SH3GL3 to decrease the stem cell-like property and tumorigenic potential. Copyright © 2021 Elsevier Inc. All rights reserved.

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出版当年[2022]版:
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
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出版当年[2021]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [a]Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China
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