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Connecting Signaling and Metabolic Pathways in EGF Receptor-Mediated Oncogenesis of Glioblastoma

Connecting Signaling and Metabolic Pathways in EGF Receptor-Mediated Oncogenesis of Glioblastoma

Arup K Bag, Sapan Mandloi, Saulius Jarmalavicius, Susmita Mondal, Krishna Kumar, Chhabinath Mandal, Peter Walden, Saikat Chakrabarti, Chitra Mandal

PLoS Comput Biol. 2019 Aug 6;15(8):e1007090.

PMID: 31386654

Abstract:

As malignant transformation requires synchronization of growth-driving signaling (S) and metabolic (M) pathways, defining cancer-specific S-M interconnected networks (SMINs) could lead to better understanding of oncogenic processes. In a systems-biology approach, we developed a mathematical model for SMINs in mutated EGF receptor (EGFRvIII) compared to wild-type EGF receptor (EGFRwt) expressing glioblastoma multiforme (GBM). Starting with experimentally validated human protein-protein interactome data for S-M pathways, and incorporating proteomic data for EGFRvIII and EGFRwt GBM cells and patient transcriptomic data, we designed a dynamic model for EGFR-driven GBM-specific information flow. Key nodes and paths identified by in silico perturbation were validated experimentally when inhibition of signaling pathway proteins altered expression of metabolic proteins as predicted by the model. This demonstrated capacity of the model to identify unknown connections between signaling and metabolic pathways, explain the robustness of oncogenic SMINs, predict drug escape, and assist identification of drug targets and the development of combination therapies.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248768	EGF-receptor human			Price

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