Collagen Prolyl Hydroxylases are Essential for Breast Cancer Metastasis
Menée à l'aide d'un modèle murin et sur des échantillons tumoraux prélevés chez des patientes atteintes d'un cancer métastatique du sein, cette étude met en évidence des mécanismes par lesquels l'expression d'une enzyme impliquée dans la synthèse du collagène, la prolyl hydroxylase, favorise le processus métastatique
Metastasis is the leading cause of death among patients with breast cancer. Understanding the role of the extracellular matrix in the metastatic process may lead to the development of improved therapies for cancer patients. Intratumoral hypoxia is found in the majority of breast cancers and is associated with an increased risk of metastasis and patient mortality. Here we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced invasion and metastasis to lymph nodes and lungs. We establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and demonstrate that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, decreases tumor fibrosis and metastasis in a mouse model of breast cancer.