Complex role of HIF in cancer: the known, the unknown, and the unexpected
Patricia Denise Tiburcio,1,2 Hyunsung Choi,1 L Eric Huang1,2
1Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA; 2Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
Abstract: Tumor hypoxia has long been recognized as a driving force of malignant progression and therapeutic resistance. The discovery of hypoxia-inducible transcription factors (HIFs) has greatly advanced our understanding of how cancer cells cope with hypoxic stress by maintaining bioenergetics through the stimulation of glycolysis. Until recently, however, it remained perplexing why proliferative cancer cells opt for aerobic glycolysis, an energy-inefficient process of glucose metabolism. Furthermore, the role of HIF in cancer has also become complex. In this review, we highlight recent groundbreaking findings in cancer metabolism, put forward plausible explanations to the complex role of HIF, and underscore remaining issues in cancer biology.
Keywords: cancer biology, hypoxia, metabolism, oncogenic signaling
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