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Hypoxia is a potent microenvironmental factor that promotes tumor metastasis. Recent studies have revealed mechanisms by which hypoxia and activation of hypoxia inducible factor (HIF)-dependent signaling promotes metastasis through the regulation of metabolic reprogramming, the stem cell phenotype, invasion, angiogenesis, immune suppression, the premetastatic niche, intravasation and/or extravasation, and resistance to apoptosis. These discoveries suggest novel paradigms in tumor metastasis and identify new opportunities for therapeutic intervention in the prevention and treatment of metastatic disease. Here, we review the impact of hypoxia and hypoxic signaling pathways in tumor and stromal cells on each step of the metastatic cascade.

Original publication

DOI

10.1016/j.trecan.2016.05.006

Type

Journal article

Journal

Trends Cancer

Publication Date

06/2016

Volume

2

Pages

295 - 304

Keywords

Animals, Cell Hypoxia, Humans, Neoplasm Metastasis, Neoplasms, Signal Transduction, Stromal Cells, Tumor Microenvironment