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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2.2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2019031365
pages 243-250

Hyperactivated Insulin Signaling Cascade in Human Glioblastoma Cells

Zhe Pei
Department of Molecular, Cellular and Biomedical Sciences, City University of New York School of Medicine, 160 Convent Avenue, New York, NY 10031, USA
Kuo-Chieh Lee
Department of Molecular, Cellular and Biomedical Sciences, City University of New York School of Medicine, 160 Convent Avenue, New York, NY 10031, USA
Amber Khan
Department of Molecular, Cellular and Biomedical Sciences, City University of New York School of Medicine, 160 Convent Avenue, New York, NY 10031, USA; Department of Biology, Neuroscience Program, Graduate School of The City University of New York, 365 Fifth Avenue, New York, NY 10061, USA
Hoau-Yan Wang
Department of Molecular, Cellular and Biomedical Sciences, City University of New York School of Medicine, 160 Convent Avenue, New York, NY 10031, USA; Department of Biology, Neuroscience Program, Graduate School of The City University of New York, 365 Fifth Avenue, New York, NY 10061, USA


Glioblastoma multiforme (GBM) is the most common and malignant glial tumor. Although pro-growth, pro-survival, and pro-metastasis insulin signaling has been proposed to be a prominent driver of GBM progression, the insulin receptor (IR) signaling cascade in GBM has not been fully elucidated. Upon binding of the insulin and insulin-like growth factor-1 (IGF-1), IR is activated by increasing the levels of tyrosine-phosphorylated (pY) IRP on tyrosine 960, 1150, and 1151 residues as well as IRS-1 recruitment to IRβ. This leads to activation of the downstream PI3K/AKT/GSK3 or mTORC1/ERK, many of which are implicated in tumorigenesis including breast and liver carcinomas. Here, we directly compare insulin signaling in U87 MG human glioblastoma to primary human astrocytes by assessing the levels of activated IRβ, IRS-1 recruitment to IRβ, as well as downstream activated mitogenic ERK2 and pro-survival AKT1 under nonstimulated conditions and induced by 1 nM insulin. Our results show insulin receptor and its downstream signaling molecules are robustly hyperactivated. This mechanism renders a reduced insulin-induced response. Our findings provide a mechanism through which GBM develops and grows aggressively even without insulin.


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