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Int J Biol Sci 2024; 20(7):2440-2453. doi:10.7150/ijbs.85984 This issue Cite

Research Paper

TSPAN6 reinforces the malignant progression of glioblastoma via interacting with CDK5RAP3 and regulating STAT3 signaling pathway

Chong Zhang^1,2,3#, Fei-hua Du^2,4#, Rou-xin Wang^2,4, Wen-bo Han², Xing Lv², Ling-hui Zeng^2,3✉, Guo-qing Chen^1✉

1. Affiliated Luqiao Hospital, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China, 310015.
2. School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China, 310015.
3. Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China, 310015.
4. Department of Pharmacology, Zhejiang University, Hangzhou, Zhejiang, China, 310058.
#Contributed equally to this work.

✉ Corresponding authors: Guo-qing Chen and Ling-hui Zeng. Address: Department of Pharmacology, School of Medicine, Hangzhou City University, No.51 Huzhou Street, Hangzhou, Zhejiang, China, 310015. E-mail: 552345085com and zenglhedu.cn; Phone: 86-0571-88013821; Fax: 86-0571-88018442. More

Abstract

Glioblastoma is the prevailing and highly malignant form of primary brain neoplasm with poor prognosis. Exosomes derived from glioblastoma cells act a vital role in malignant progression via regulating tumor microenvironment (TME), exosomal tetraspanin protein family members (TSPANs) are important actors of cell communication in TME. Among all the TSPANs, TSPAN6 exhibited predominantly higher expression levels in comparison to normal tissues. Meanwhile, glioblastoma patients with high level of TSPAN6 had shorter overall survival compared with low level of TSPAN6. Furthermore, TSPAN6 promoted the malignant progression of glioblastoma via promoting the proliferation and metastatic potential of glioblastoma cells. More interestingly, TSPAN6 overexpression in glioblastoma cells promoted the migration of vascular endothelial cell, and exosome secretion inhibitor reversed the migrative ability of vascular endothelial cells enhanced by TSPAN6 overexpressing glioblastoma cells, indicating that TSPAN6 might reinforce angiogenesis via exosomes in TME. Mechanistically, TSPAN6 enhanced the malignant progression of glioblastoma by interacting with CDK5RAP3 and regulating STAT3 signaling pathway. In addition, TSPAN6 overexpression in glioblastoma cells enhanced angiogenesis via regulating TME and STAT3 signaling pathway. Collectively, TSPAN6 has the potential to serve as both a therapeutic target and a prognostic biomarker for the treatment of glioblastoma.

Keywords: TSPAN6, glioblastoma, angiogenesis, STAT3, CDK5RAP3

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