Intersectin1-s, A Multidomain Adapter Protein, Is Essential for Malignant Glioma Proliferation

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