Daniele Gilkes, Ph.D. Research Assistant Professor Dept. of Chemical & Biomolecular Engineering Johns Hopkins University

Hypoxia and The Extracellular Matrix: Drivers of Breast Cancer Metastasis

Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that low oxygen tension (hypoxia), which occurs in most solid tumors, alters the biophysical and biochemical parameters of the extracellular matrix within a tumor. Our work demonstrates that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of extracellular matrix remodeling (ECM) under hypoxic conditions. HIF-1 activates expression of genes encoding collagen prolyl (P4HA1 and P4HA2) and lysyl (PLOD2) hydroxylase enzymes. P4HA1 and P4HA2 are required for collagen deposition, whereas PLOD2 is required for ECM stiffening and collagen fiber alignment. Together P4HA1, P4HA2, and PLOD2 mediate ECM remodeling to provide architectural and chemical cues that induce changes in breast cancer cell morphology, adhesion, and motility to promote invasion and metastasis.

Location
1005 GBSF