cIAP1 regulates the EGFR/Snai2 axis in triple negative breast cancer cells

Inhibitor of apoptosis (IAP) proteins constitute a conserved family of molecules which regulate both apoptosis and receptor signaling. They are often deregulated in cancer cells and represent potential targets for therapy. In our work, we investigated the effect of IAP inhibition in vivo to identify novel downstream genes expressed in an IAP-dependent manner that could contribute to cancer aggressiveness. To this end, immunocompromised mice engrafted subcutaneously with the triple negative breast cancer MDA-MB231 cell line were treated with SM83, a pan-IAP inhibitor developed by us, and tumor nodules were profiled for gene expression. Our work suggests that IAP-targeted therapy could contribute to EGFR inhibition and the reduction of its downstream mediators. This approach could be particularly effective in cells characterized by high levels of EGFR and Snai2, such as triple negative breast cancer. Experiments were approved by the Ethics Committee for Animal Experimentation of the Istituto Nazionale Tumori (INT) of Milan according to institutional guidelines and by the Italian Minister of Health. NOD/SCID mice were subcutaneously engrafted with 5x10^6 MDA-MB231 and MDA-MB468 cells and, after two weeks, were treated with 5 mg/Kg SM83 injected intraperitoneally 5 times/week for 2 weeks (MDA-MB231 model).