Epigenetic drivers of metalloproteinases and metastasis.

Abstract

Metalloproteinases (MPs) are crucial for development and homeostasis due to their diverse physiological functions, from the cellular to the organismal level. Their activity is tightly regulated at multiple levels, including epigenetic regulation through DNA methylation and histone modifications. Aberrant MP expression can result in pathological events, involving extracellular matrix remodeling, which can facilitate cancer cell invasion and dissemination. As clinical testing of MP inhibitors has been limited by toxicity, alternative approaches are needed. Epigenetically-driven MP expression is often specific to cancer cells, giving an enticing possibility for cancer cell-specific targeting. Moreover, aberrant epigenetic activity can also drive other metastatic events. Therefore, targeting the epigenetic regulators of MP expression may be a promising alternative approach for the prevention and treatment of metastatic disease.