Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity - PubMed (original) (raw)

Review

Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity

Jin Qian et al. Adv Exp Med Biol. 2019.

Abstract

Intratumoral heterogeneity is an important factor contributing to metastasis and therapy resistance. The phenotypic diversity of cancer cells within the tumor microenvironment is strongly influenced by microenvironmental factors such as hypoxia. Clinically, hypoxia and the hypoxia inducible transcription factors HIF-1 and HIF-2 are associated with cancer stem cells, metastasis and drug resistance in multiple tumor types. Experimental models have demonstrated an important functional role for HIF signaling in driving CSC, metastatic and drug resistant phenotypes in vitro and in vivo. Here we will review recent studies that highlight novel mechanisms by which hypoxia promotes cancer stem cell, metastatic and drug resistant phenotypes.

Keywords: Cancer stem cell; Chemotherapy; HIF; Hypoxia; Metabolism; Metastasis; Stemness; Therapy resistance.

PubMed Disclaimer

Figures

Fig. 3.1

Fig. 3.1. Mechanisms of hypoxia induced tumor heterogeneity.

The hypoxic tumor microenvironment facilitates cancer stem cell, metastatic and therapy resistant phenotypes through multiple mechanisms. Both HIF-dependent and independent mechanisms drive the selection of cancer stem cells within the hypoxic tumor microenvironment that contribute to metastatic disease and therapy relapse. Additionally, the selection of chemoresistant clones can stabilize HIF under normoxic conditions to further promote stemness and metastatic phenotypes

References

    1. Shibue T, Weinberg RA (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 14:611–629. 10.1038/nrclinonc.2017.44 - DOI - PMC - PubMed
    1. Brown JM, Giaccia AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58:1408–1416 - PubMed
    1. Oskarsson T, Batlle E, Massague J (2014) Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell 14:306–321. 10.1016/j.stem.2014.02.002 - DOI - PMC - PubMed
    1. Jaakkola P et al. (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292: 468–472. doi: 10.1126/science.1059796 1059796 [pii] - DOI - PubMed
    1. Rankin EB, Giaccia AJ (2008) The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 15: 678–685. doi: cdd200821 [pii] 10.1038/cdd.2008.21 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources