Estudio del remodelado de la homeostasis del calcio intracelular en las células de cáncer de mama

Abstract

The Store Operated Calcium Entry (SOCE) is a ubiquitous signalling mechanism that controls a wide variety of cellular functions. Although STIM and Orai protein families are the molecular mediators of SOCE, a large number of auxiliary proteins have been involved in the events of SOCE activation and inhibition. In 2020, with 2,3 million new cases, female breast cancer was the most commonly diagnosed cancer. Within the physiopathology of breast cancer the communication mechanisms based on calcium, and especially SOCE, are consider crucial events for the control and development of breast cancer cell hallmarks. In this Thesis, we expand our understanding about the role of adenylyl cyclase 8 and filamin A in the regulatory mechanisms of SOCE. Furthermore, we prove that adenylyl cyclase 8 promotes the proliferative and migratory capacity of triple negative breast cancer cells, role that is mediated by the impairment of the inhibitory mechanism of SOCE. Finally we have described the role of TRPC6 in the maintenance of calcium haemostasis in estrogen receptor positive breast cancer cells. This function enables the reduction of reticular stress in breast cancer cells and impairs the onset of the apoptotic mechanism.