Rosalba Camicia
University of Zurich
Switzerland
Title: B-aggressive lymphoma proteins BALs and IFNγ /STAT signaling pathway: new drug targets in highly chemo-resistant tumors
Biography
Biography: Rosalba Camicia
Abstract
The B-aggressive lymphoma proteins BALs have been recently identified as a risk-related gene product in aggressive diffuse large B-cell lymphoma (DLBCL) and Prostate cancer (PCa). BALs are constitutively expressed in a subset of high-risk DLBCLs with an active host inflammatory response and have been suggested to be associated with interferon-related gene expression. We have previously demonstrated that BAL1 acts as a novel oncogenic survival factor in high-risk, chemo-resistant, diffuse large B cell lymphoma (DLBCL) (Camicia R. et Al, JCS 2013) and in metastatic PCa (Bachmann et Al., Mol Cancer 2014). Our study provides first evidence that the enzymatic activity of BALs is required for survival of diffuse large B cell lymphoma (DLBCL) and mPCa cells. Our results show for the first time that BAL1 represses the anti-proliferative and pro-apoptotic IFNγ-STAT1-IRF1-p53 axis and mediates proliferation, survival and chemo-resistance in DLBCL and mPCa. As a consequence constitutive IFNγ-STAT1 signaling does not lead to apoptosis but rather to chemo-resistance in tumors overexpressing BALs. The present study further suggests that the combined targeted inhibition of STAT1, BAL1 and BAL2 could increase the efficacy of chemotherapy or radiation treatment in DLBCL, prostate cancer and other high-risk tumor types with an increased STAT1 signaling.
