Uncovering the Role of TRPM2 in TNBC

Abstract

Breast cancer has high mortality in women worldwide and is a complex disease. Specifically, TNBC is an aggressive subtype which lacks a unique therapeutic target. Cancer cells have higher ROS, however the mechanism by which they regulate cancer survival remains unknown. TRPM2 is a sensor of oxidative stress and Ca2+ permeable ion channel, previously associated with cancer development. We hypothesize that elevated oxidative stress activates TRPM2 mediated Ca2+ signaling to supply cancer cell bioenergetics and fuel TNBC progression. Our study found that TRPM2-KD reduced proliferation, migration and mitophagy and increased apoptosis in TNBC cells. We identified p-CAMKII as the signaling molecule which links TRPM2 mediated Ca2+, to downstream JNK and FAK signaling. Altogether, our study proposes a potential mechanism to explain the role of TRPM2 mediated Ca2+ signaling in control of TNBC survival and suggests that it could function as a specific therapeutic target for TNBC in the future.