Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity

Jin Qian; Erinn B Rankin

doi:10.1007/978-3-030-12734-3_3

Hypoxia-Induced Phenotypes that Mediate Tumor Heterogeneity

Adv Exp Med Biol. 2019:1136:43-55. doi: 10.1007/978-3-030-12734-3_3.

Authors

Jin Qian¹, Erinn B Rankin^{2

3}

Affiliations

¹ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. erankin@stanford.edu.
³ Department of Obstetrics & Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA, USA. erankin@stanford.edu.

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.

Publication types

Review

MeSH terms

Basic Helix-Loop-Helix Transcription Factors
Cell Hypoxia
Cell Line, Tumor
Drug Resistance, Neoplasm
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Neoplasms / pathology*
Neoplastic Stem Cells / cytology*
Phenotype
Tumor Hypoxia*

Substances

Basic Helix-Loop-Helix Transcription Factors
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
endothelial PAS domain-containing protein 1

Grants and funding

R01 CA198291/CA/NCI NIH HHS/United States