Mixed Lineage Kinase 2 (MLK2) in tumor angiogenesis

Brigham And Women'S Hospital, Boston MA

Investigators

Abstract

Project Summary Cancer is one of the leading causes of death in the USA. The study examines the role of Mixed Lineage Kinase 2 (MLK2) in tumor angiogenesis, a process vital for cancer growth. Hypoxic condition in solid tumor activates stress pathway of MLK2. MLK2, abundantly present in the endothelium, is shown to be essential for endothelial proliferation, migration, and angiogenesis. Lack of MLK2 impairs tumor growth in mouse models and increases miR-146a levels, which suppresses angiogenic factors like VEGF, adversely affecting angiogenesis and endothelial cell proliferation. Given that miR-146a overexpression in endothelial cells leads to similar deficiencies, the study suggests that MLK2's regulatory effect on miR-146a is crucial for endothelial functions and tumor angiogenesis.