MMPs, tyrosine kinase signaling and extracellular matrix proteolysis in kidney cancer.

Patients diagnosed with metastatic renal cell carcinoma (RCC) have ∼12% chance for 5-year survival. The integrity of the extracellular matrix (ECM) that surrounds tumor cells influences their behavior and, when disturbed, it could facilitate local invasion and spread of tumor cells to distant sites. The interplay between von Hippel-Lindau/hypoxia inducible factor signaling axis and activated kinase networks results in aberrant ECM and tumor progression. Matrix metalloproteinases (MMPs) are proteolytic enzymes implicated in ECM remodeling, tumor angiogenesis, and immune cell infiltration. Understanding the cross-talk between kinase signaling and ECM proteolysis in RCC could provide insights into developing drugs that interfere specifically with the process of invasion. In this review, we discuss changes in the MMPs/ECM axis in RCC, prominent kinase signaling pathways implicated in MMPs induction, and comment on emerging extracellular regulatory networks that modulate MMPs activity.