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TSPAN4 influences glioblastoma progression through regulating EGFR stability

Authors :
Yanbin Dong
Xiaolong Tang
Wenhui Zhao
Ping Liu
Weiru Yu
Jinlai Ren
Yu Chen
Yanfang Cui
Juan Chen
Yongshuo Liu
Source :
iScience, Vol 27, Iss 8, Pp 110417- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: 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.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
8
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.77618813a0934ae0954e0a0b585de10b
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.110417