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Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Hypoxia is a potent microenvironmental factor promoting metastatic progression. Clinically, hypoxia and the expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 are associated with increased distant metastasis and poor survival in a variety of tumor types. Moreover, HIF signaling in malignant cells influences multiple steps within the metastatic cascade. Here we review research focused on elucidating the mechanisms by which the hypoxic tumor microenvironment promotes metastatic progression. These studies have identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at preventing and treating metastatic disease.

Original publication

DOI

10.1126/science.aaf4405

Type

Journal article

Journal

Science

Publication Date

08/04/2016

Volume

352

Pages

175 - 180

Keywords

Animals, Basic Helix-Loop-Helix Transcription Factors, Biomarkers, Tumor, Cell Hypoxia, Cell Movement, Disease Progression, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasm Invasiveness, Neoplasm Metastasis, Radiation Tolerance, Signal Transduction, Tumor Microenvironment