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Review
. 2019:1136:43-55.
doi: 10.1007/978-3-030-12734-3_3.

Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity

Jin Qian  1 , Erinn B Rankin  2   3
Affiliations
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.

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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
See this image and copyright information in PMC

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