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Intersectin1‐s, A multidomain adapter protein, Is essential for malignant glioma proliferation
Author(s) -
Gu Feng,
Zhang Huikun,
Qin Fengxia,
Liu Xiaoli,
Li Wenliang,
Fu Li,
Ying Guoguang,
Li Binghui,
Zhang Ming,
Ma Yongjie
Publication year - 2015
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22830
Subject(s) - glioma , biology , signal transducing adaptor protein , cancer research , endocytosis , cell growth , exocytosis , mapk/erk pathway , microbiology and biotechnology , glioblastoma , signal transduction , cell , secretion , genetics , biochemistry
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. GLIA 2015;63:1595–1605