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TSPAN4 influences glioblastoma progression through regulating EGFR stability

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机构: [1]Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. [2]Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China. [3]Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China. [4]Department of Clinical Laboratory, The Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University, Lianyungang, Jiangsu 222042, China. [5]Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
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Glioblastoma (GBM) is characterized by high morbidity, mortality, and low cure rates. Recent studies suggest that TSPAN4 is recognized as a marker protein for migrasomes, a vesicular organelle associated with cell migration. However, the intrinsic role of TSPAN4 in cancers has not been clarified, especially in GBM. Here, we report that TSPAN4 promotes GBM progression by interacting with epidermal growth factor receptor (EGFR) and regulating its stability. Clinically, TSPAN4 is highly expressed in GBM and is significantly correlated with poor prognosis. Functionally, TSPAN4 knockdown dramatically inhibits GBM cell proliferation and invasion in vitro, as well as tumorigenicity in vivo. Conversely, overexpression of TSPAN4 facilitates GBM progression. Mechanistically, TSPAN4 knockdown disrupts interaction with EGFR, destabilizing its expression and inactivating EGFR and downstream signaling pathways, such as MEK/ERK, STAT3, and AKT. Our study reveals that TSPAN4 drives GBM progression through regulating EGFR stability and could be a potential target for cancer therapy.© 2024 The Authors.

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出版当年[2023]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2023]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
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第一作者机构: [1]Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. [2]Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.
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