Hypoxia and hypoxia-inducible factors (HIFs): master regulators of metastasis
By Xin Lu, Yibin Kang. Clinical Cancer Research, 2010
669 citations recorded by the source corpus.
Hypoxia is a common condition found in a wide range of solid tumors and is often associated with poor prognosis. Hypoxia increases tumor glycolysis, angiogenesis, and other survival responses, as well as invasion and metastasis by activating relevant gene expressions through hypoxia-inducible factors (HIF). HIF-1α and HIF-2α undergo oxygen-dependent regulation, and their overexpression is frequently associated with metastasis and poor clinical outcomes. Recent studies show that each step of the metastasis process, from the initial epithelial-mesenchymal transition to the ultimate organotropic colonization, can potentially be regulated by hypoxia, suggesting a master regulator role of hypoxia and HIFs in metastasis. Furthermore, modulation of cancer stem cell self-renewal by HIFs may also contribute to the hypoxia-regulated metastasis program. The hypoxia-induced metastatic phenotype may be one of the reasons for the modest efficacy of antiangiogenic therapies and may well explain the recent provocative findings that antiangiogenic therapy increased metastasis in preclinical models. Multiple approaches to targeting hypoxia and HIFs, including HIF inhibitors, hypoxia-activated bioreductive prodrugs, and gene therapies may become effective treatments to prevent or reduce metastasis. Clin Cancer Res; 16(24); 5928–35 ©2010 AACR.
Subfields: Biotechnology, Cancer Research, Hepatology
View Paper: https://www.semanticscholar.org/paper/b595029230e64e1137d871fd8f97bad6143c8cd2
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In Cancer Research
Citations in the corpus
- The Pancreas Cancer Microenvironment (2012, neutral): “tion of many angiogenic growth factors (84).”
- Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia (2012, background): “The administration of antiangiogenic agents has been shown to generate intratumoral hypoxia, and hypoxia has been shown to modulate each step in the metastatic process (8).”
- Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis. (2018, background): “Hypoxia is one of the important features in solid tumors and exosomes, once secreted, could deliver biologic information by internalization to neighboring or distant cells (8, 11).”
- Signaling mechanisms of the epithelial-mesenchymal transition (2014, background): “Under hypoxic conditions, PHDs are inactivated, thus enabling the accumulation and functional activation of HIF-1a, which induces the expression of genes associated with EMT, such as TGF-b, TWIST, and LOX, and the stabilization of the Snail1/2 transcriptional repressors.”