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Int J Mol Sci. 2017 Jan 18;18(1). pii: E189. doi: 10.3390/ijms18010189.

Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer.

Author information

1
Department of Chemistry and Biology, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3, Canada. rehman.ata@ryerson.ca.
2
Graduate Program in Molecular Science, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3, Canada. rehman.ata@ryerson.ca.
3
Department of Chemistry and Biology, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3, Canada. cantonescu@ryerson.ca.
4
Graduate Program in Molecular Science, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3, Canada. cantonescu@ryerson.ca.
5
Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON M5B 2K3, Canada. cantonescu@ryerson.ca.

Abstract

Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions. In this review, we examine the control of integrin function by cell metabolism, and the impact of this regulation in cancer. Within this context, nutrient sufficiency or deprivation is sensed by a number of metabolic signaling pathways such as AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) 1, which collectively control integrin function by a number of mechanisms. Moreover, metabolic flux through specific pathways also controls integrins, such as by control of integrin glycosylation, thus impacting integrin-dependent cell adhesion and migration. Integrins also control various metabolic signals and pathways, establishing the reciprocity of this regulation. As cancer cells exhibit substantial changes in metabolism, such as a shift to aerobic glycolysis, enhanced glucose utilization and a heightened dependence on specific amino acids, the reciprocal regulation of integrins and metabolism may provide important clues for more effective treatment of various cancers.

KEYWORDS:

AMPK; HIF1; cancer metabolism; glycosylation; hypoxia; mTOR; membrane traffic; metabolic stress; nutrient deficit

PMID:
28106780
PMCID:
PMC5297821
DOI:
10.3390/ijms18010189
[Indexed for MEDLINE]
Free PMC Article

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