Hypoxia and metabolic adaptation of cancer cells

By Katherine L. Eales, Kate E. R. Hollinshead, Dan A. Tennant. Oncogenesis, 2016

668 citations recorded by the source corpus.

Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7fcfd6a9fa79c449033e13238845afb93e57e5fb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems (2017, background): “Such a system could potentially activate and deactivate to keep a tumor cell population in control, and to reduce hypoxia (which is known to drive cancer cell adaptation to more aggressive phenotypes [42, 43]).”
Metabolic Instruction of Immunity (2017, positive): “When tumor growth exceeds the vasculature’s ability to fully perfuse the tumor microenvironment with oxygen, regions of hypoxia are established and induction of the hypoxia-responsive transcription factor HIF-1α intensifies cancer cell glucose utilization and lactate release (Eales et al., 2016).”