title: Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression.
abstract: Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma.
authors: Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors: Si-Jian
authors: SJ
authors: Pan
authors: Department of Internal Medicine Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079, China.
authors: Yue-Bing
authors: YB
authors: Wu
authors: Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 21500, China.
authors: Shang
authors: S
authors: Cai
authors: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Yi-Xin
authors: YX
authors: Pan
authors: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Wei
authors: W
authors: Liu
authors: Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors: Liu-Guan
authors: LG
authors: Bian
authors: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Bomin
authors: B
authors: Sun
authors: Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: sunqingfang11@163.com.
authors: Qing-Fang
authors: QF
authors: Sun
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D060787:Neoplasm Grading; D034622:RNA Interference; D000077204:Temozolomide; D059470:Tetraspanins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018906:Antineoplastic Agents, Alkylating; C065609:TSPAN8 protein, human; D059470:Tetraspanins; D003606:Dacarbazine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000077204:Temozolomide
keywords: Focal adhesion kinase; Malignant glioma; Migration; Proliferation; Temozolomide resistance; Tetraspanin 8