Procollagen lysyl hydroxylase 2 is essential for hypoxia-induced breast cancer metastasis

Daniele M. Gilkes, Saumendra Bajpai, Carmen C. Wong, Pallavi Chaturvedi, Maimon E. Hubbi, Denis Wirtz, Gregg L. Semenza

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis is the leading cause of death among patients who have breast cancer. Understanding the role of the extracellular matrix (ECM) in the metastatic process may lead to the development of improved therapies to treat patients with cancer. Intratumoral hypoxia, found in the majority of breast cancers, is associated with an increased risk of metastasis and mortality. We found that in hypoxic breast cancer cells, hypoxia-inducible factor 1 (HIF-1) activates transcription of the PLOD1 and PLOD2 genes encoding procollagen lysyl hydroxylases that are required for the biogenesis of collagen, which is a major constituent of the ECM. High PLOD2 expression in breast cancer biopsies is associated with increased risk of mortality. We show that PLOD2 is critical for fibrillar collagen formation by breast cancer cells, increases tumor stiffness, and is required for metastasis to lymph nodes and lungs.

Original languageEnglish (US)
Pages (from-to)456-466
Number of pages11
JournalMolecular Cancer Research
Volume11
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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