TY - JOUR
T1 - Hypoxia-inducible factors
T2 - cancer progression and clinical translation
AU - Wicks, Elizabeth E.
AU - Semenza, Gregg L.
N1 - Funding Information:
GLS is an American Cancer Society Research Professor and the C. Michael Armstrong Professor at the Johns Hopkins University School of Medicine. Work in GLS’s laboratory is supported by the Armstrong Family Foundation. EEW is a Sarnoff Cardiovascular Research Foundation Fellow.
Publisher Copyright:
Copyright: © 2022, Wicks et al.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis. In this Review, the mechanisms and consequences of HIF activation in cancer cells are presented. The current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.
AB - Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis. In this Review, the mechanisms and consequences of HIF activation in cancer cells are presented. The current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.
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U2 - 10.1172/JCI159839
DO - 10.1172/JCI159839
M3 - Review article
C2 - 35642641
AN - SCOPUS:85131209049
SN - 0021-9738
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
M1 - e159839
ER -