HIF1α and HIF2α: sibling rivalry in hypoxic tumor growth and progression

By B. Keith, Randall S. Johnson, M. C. Simon. Nature Reviews. Cancer, 2011

1,557 citations recorded by the source corpus.

Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a52ad56a5dfe5c3205ed2376bed9a66ed12b73a5

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

1. David M. Sabatini
2. V. Nizet
3. Russell G. Jones
4. B. Faubert
5. A. Palazón
6. Richard J. Johnson
7. C. Wigerup
8. Ananda W. Goldrath

In Molecular Biology

1. David M. Sabatini
2. M. Laplante
3. Ralph J. Deberardinis
4. Russell G. Jones
5. B. Faubert
6. P. Siegel
7. Richard J. Johnson
8. C. Wigerup

In Oncology

1. David M. Sabatini
2. Russell G. Jones
3. M. Laplante
4. Ralph J. Deberardinis
5. V. Nizet
6. J. Massagué
7. R. Shaw

Citations in the corpus

• Regulation of mTORC1 and its impact on gene expression at a glance (2013, background): “The increase in HIF1a activity, which results from oncogenic activation and/or intratumoral hypoxia, has been associated with an increased patient mortality in several types of cancer (reviewed by Keith et al., 2012).”
• THE HISTONE DEACETYLASE SIRT6 IS A NOVEL TUMOR SUPPRESSOR THAT CONTROLS CANCER METABOLISM (2012, neutral): “Moreover, HIF-1 α and HIF-2 α have overlapping functions, and how these two factors influence tumorigenesis remains still highly controversial (Keith et al., 2012).”
• From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, neutral): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
• AMPK is a negative regulator of the Warburg Effect and suppresses tumor growth in vivo (2012, background): “Several of the enzymes elevated in AMPKa-deficient cells are known targets of the transcription factor HIF-1a, one of the central regulators of glycolysis induced by hypoxia (Keith et al., 2012; Semenza, 2011).”
• HIF Transcription Factors, Inflammation, and Immunity (2014, background): “As has been shown in cancer cells (Holmquist-Mengelbier et al., 2006; Keith et al., 2012; Warnecke et al., 2008), differing expression patterns of the HIF-1a and HIF-2a isoforms in immune cells depend on both intrinsic and extrinsic factors, and their resulting balance specifically contributes to…”
• Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. (2016, background): “A comprehensive description of HIF-α regulation and the conflicting roles of HIF-1α and HIF-2α are given in Keith et al. (2012).”
• ANTIANGIOGENESIS STRATEGIES REVISITED: FROM STARVING TUMORS TO ALLEVIATING HYPOXIA (2014, neutral): “…a protumorigenic and immunosuppressive phenotype (Casazza et al., 2014; Colegio et al., 2014; Finger and Giaccia, 2010; Hanahan and Coussens, 2012; Keith et al., 2012; Motz and Coukos, 2013; Noy and Pollard, 2014; Cancer Cell 26, November 10, 2014 ª2014 Elsevier Inc. 605 NS, not significant;…”