Abstract 2476: The oncogenic role of p63 in altered-FGFR3 bladder tumors

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.2476-2476
• Main Authors: Zambrano, Macarena, Moreno-Vega, Aura I., Dufour, Florent, Sciacca, Marianela, Langle, Yanina V., Radvanyi, François, Eiján, Ana M., Bernard-Pierrot, Isabelle, Lodillinsky, Catalina
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-2476

Recently, a new classification of muscle-invasive bladder cancer (MIBCs) has been proposed (Kamoun, 2020). There are 6 classes of MIBC: the over-expression or activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with luminal subtypes. As typically expected, basal tumors exhibit increased TP63 activity, but interestingly, this is also observed in luminal-papillary (LumP) tumors. LumP are enriched in both, FGFR3 mutations and p63 activation. The regulatory gene pathways and p63 functional role in these tumors remains poorly characterized. Therefore, this is our main objective, together with the study of the link with FGFR3 mutations. We hypothesize that p63 drives a protumoral program in bladder cancer (BC) commanded by the regulation of altered FGFR3. We used human BC cell lines bearing FGFR3 mutations with inducible silencing for p63 in order to identify the functional role of p63 in this context. Loss of p63 led to a decreased 2D and 3D growth (p