The role of GSK3 in metabolic pathway perturbations in cancer
David Papadopoli1, Michael Pollak2, Ivan Topisirovic3
1Lady Davis Institute for Medical Research, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada; Gerald Bronfman Department of Oncology, McGill University, 5100 Maisonneuve Blvd West, Montréal, QC H4A 3T2, Canada.
Abstract:
Malignant transformation and tumor progression are accompanied by significant perturbations in metabolic programs. As such, cancer cells support high ATP turnover to construct the building blocks needed to fuel neoplastic growth. The coordination of metabolic networks in malignant cells is dependent on the collaboration with cellular signaling pathways. Glycogen synthase kinase 3 (GSK3) lies at the convergence of several signaling axes, including the PI3K/AKT/mTOR, AMPK, and Wnt pathways, which influence cancer initiation, progression and therapeutic responses. Accordingly, GSK3 modulates metabolic processes, including protein and lipid synthesis, glucose and mitochondrial metabolism, as well as autophagy. In this review, we highlight current knowledge of the role of GSK3 in metabolic perturbations in cancer.
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