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Critical Reviews™ in Oncogenesis
Главный редактор: Benjamin Bonavida (open in a new tab)

Выходит 4 номеров в год

ISSN Печать: 0893-9675

ISSN Онлайн: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

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Hyperactivated Insulin Signaling Cascade in Human Glioblastoma Cells

Том 24, Выпуск 3, 2019, pp. 243-250
DOI: 10.1615/CritRevOncog.2019031365
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Краткое описание

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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ЦИТИРОВАНО В
  1. Tirrò Elena, Massimino Michele, Romano Chiara, Martorana Federica, Pennisi Maria Stella, Stella Stefania, Pavone Giuliana, Di Gregorio Sandra, Puma Adriana, Tomarchio Cristina, Vitale Silvia Rita, Manzella Livia, Vigneri Paolo, Prognostic and Therapeutic Roles of the Insulin Growth Factor System in Glioblastoma, Frontiers in Oncology, 10, 2021. Crossref

  2. Li Tingting, Hentschel Andreas, Ahrends Robert, Analytical comparison of absolute quantification strategies to investigate the insulin signaling pathway in fat cells, PROTEOMICS, 22, 7, 2022. Crossref

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