Inhibition of Percupine has a differential impact on the gene expression signature of breast cancer cell lines of different levels of agrressiveness

SOFIA VALLA; GIANINA DEMARCHI; NADIA BONADEO; AGUSTINA CHIMENTO; LUCIA ROMANO; ALANIZ LAURA D; MARTIN GÖTTE

Mar del Plata

Congreso; Reunión anual de Sociedades Biocientíficas; 2019

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad de Farmacología Experimental (SAFE), la Sociedad Argentina de Biología (SAB), la Sociedad Argentina de Protozoología (SAP), la Asociación Argentina de Nanomedicinas (NANOMED-ar), La Asociaci

Aggressiveness of the BC cell lines, we analyzed the impact of IWP-2, a PORCN inhibitor, on the TNBC cell line MDA-MB-231 and in the less aggressive MCF-7 cell line. Wnt pathway is involved in cellular processes which are dysregulated in cancer as cell renewal, proliferation and EMT. In particular, in breast cancer (BC) it has a role in both tumor initiation and progression. Porcupine?s palmitoylation of Wnt ligands is required for their proper signaling and release and its inhibition showed anti-tumoral effects on different BC models. In order to study if the inhibition of Porcupine (PORCN) had different effects regarding to the aggressiveness of the BC cell lines, we analyzed the impact of IWP-2, a PORCN inhibitor, on the TNBC cell line MDA-MB-231 and in the less aggressive MCF-7 cell line. Our results show that PORCN inhibition with IWP-2 induced a different expression signature of Wnt pathway, Cell Cycle and EMT related genes in both cell lines, although it was similar regarding Stem Cell markers. Moreover, in both cell lines it reduced β-CATENIN protein levels. The stronger effects observed in CFA and Cell Viability in MDA-MB-231 cells could be explained by changes in other cellular processes as apoptosis. These results suggest that the differences in the genetic background and phenotype of breast cancer cells can modulate