title: Intersectin1-S, a multidomain adapter protein, is essential for malignant glioma proliferation.
abstract: Glioblastomas, the most aggressive form of primary brain tumors with a tendency to invade surrounding healthy brain tissues, remains an incurable disease. Intersectin (ITSN) is a multidomain adapter protein implicated in endocytosis, exocytosis, and multiple signaling pathways. Prior research of ours has shown intersectin1-S (ITSN1-S) is critical for the migration and invasion of glioma cells by regulating several key proteins. In this study, we established ITSN1-S expression patterns in human tumor tissues. We discovered that ITSN1-S expression was positively correlated with histological grade of gliomas and with poor patient prognosis. We also found that the expression of ITSN1-S protein was essential to glioblastoma cell proliferation. Furthermore, through a series of expression constructs encoding different ITSN1-S domains, we identified the critical roles of ITSN1-S SH3 domains in the regulation of cell proliferation. This study also demonstrates evidence suggesting that the regulation of ITSN1-S on glioblastoma cells proliferation is through the Raf/MEK/ERK pathway. In conclusion, this study suggests critical roles of ITSN1-S in malignant glioma proliferation, indicating a potential usage of ITSN1-S in the therapeutic intervention as a novel molecular target.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Huikun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Qin
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Ying
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Binghui
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Bioinformatics, University of Georgia, Athens, Georgia.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, People's Republic of China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Ma
mesh_terms: D016475:3T3 Cells; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D049109:Cell Proliferation / Q000502:physiology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D055815:Young Adult
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; C485568:ITSN1 protein, human
keywords: ITSN1 isoforms; ITSN1-S; SH3 domain; cell proliferation; glioblastoma; signaling pathway