Study of the role of focal adhesion kinase on DNA damage response in cardiomyocytes submitted to genotoxic stress using structured illumination miscroscopy

Abstract

Cardiovascular complications of anticancer chemotherapy are emerging as a major issue in public health, considering the increase in the cancer survival rate during last years. Cardiotoxicity caused by chemotherapeutics as doxorubicin (doxo), is a serious condition, that can evolve to chronic cardiomyopathy, congestive heart failure and patient death. Studies focused on the signaling activated by anticancer chemotherapy have shown the importance of focal adhesion kinesin to the cellular survival and to the resistance to this treatment, however, this signaling process is not fully understood yet. The present proposal aims to characterize the effects of this treatment with doxo in the subcellular redistribution of FAK in cardiac myocytes H9C2. Futhermore, we will investigate if FAK co-localizes with proteins related to DNA damage response after doxo treatment, such as DNA-PK, XRCC5 and DDX5, which have been previously identified in co-immunopreciptation experiments with FAK. Our findings could contribute to the understanding of these mechanisms promoted by FAK that results in cellular survival after doxo treatment and to the establishment of new therapeutic treatments for cancer with less harmful effects to the cardiac function. (AU)