Elucidating calpain’s role in the breast cancer cell signalling network

Background Improved outcomes for breast cancer patients include the use of novel targeted agents acting on key survival and proliferation pathways. Calpain is an intracellular calcium regulated protease with two predominant isoforms, calpain 1 and calpain 2. The cleavage of target proteins by calpain 1 or 2 regulates their cellular functions, including proliferation, survival and migration. We hypothesize that different survival outcomes in cancer cells in response to various therapeutics relate to distinct profiles of signaling proteins being cleaved by calpain. Thus, inhibition of calpain could interact additively or synergistically with specific therapeutics to improve breast cancer outcomes. To realize this possibility, it is essential to identify profiles of calpain targets cleaved upon challenge with specific therapeutics and determine the functional effects of calpain-mediated cleavage.