Roles of Adamalysine in extracellular matrix remodeling
Tumour microenvironment is now recognized to play a major role in growth, tumour invasion and resistance to chemotherapy. Understanding the mechanisms that regulate communication between tumour cells and this microenvironment is essential for the development of effective therapies. In this context, the Adamalysin family of proteins (ADAM for A Disintegrin And Metalloproteinase; ADAMTS for ADAM with ThromboSpondin motives and ADAMTSL for ADAMTS-like) are now important players in tumour progression by acting on extracellular matrix remodeling and the bioavailability of cell communication mediators such as cytokines, chemokines and growth factors. In recent years, our group has demonstrated an association between the overexpression of two proteins in this family, ADAM12 and ADAMTS1, and the aggressiveness of hepatocellular carcinoma. From a mechanical point of view, we have shown that these proteins regulate the activity of the growth factor TGF-, a key element of tumor progression that induces epithelio-mesenchymal transition (TEM), proliferation and cell invasion.
ADAM12L protein interaction network