O081 Investigating the FLYWCH1/ β-catenin signalling in pancreatic cancer

Abstract

Abstract Introduction β-catenin is a protein molecule of the E-cadherin/catenin adhesion complex that maintains epithelial cell-cell adhesion and intracellular signalling. The mutation and overexpression of β-catenin leads to cancer, including pancreatic ductal adenocarcinoma (PDAC). FLYWCH1 is a newly identified protein with zinc-finger type DNA-binding domain that interacts with nuclear β-catenin, leading to increased cell-cell and cell-matrix adhesion in cancer and stem cells. This study aimed to explore the roles of crosstalk between FLYWCH1 and Wnt/β-catenin signalling for the first time in pancreatic cancer cells. Methods We performed Western Blot analysis for the extraction of FLYWCH1/β-catenin, E-cadherin and GSK3-b in AsPc-1, PANC-1, and MIA PaCa-2 pancreatic cancer cell lines. Recommended concentrations of antibodies were used for the detection of proteins of interest. Tubulin was used as a loading control. Fluorescent detection was used, and the density of detected proteins were measured. Results Our results demonstrate evidence of differential expression of FLYWCH1 in pancreatic cancer cells. PANC-1 had less expression of FLYWCH1, but expression was moderate in AsPC-1. E-cadherin, β catenin, and GSK3-b were also expressed. These data suggest that FLYWCH1 levels correlated with unphosphorylated β-catenin to suppress the transcriptional product via controlling the aberrant Wnt/β-catenin pathway while E-cadherin promoted the cell-cell attachment. Conclusion These results suggest that Wnt1/β-catenin activity is negatively correlated with FLYWCH1 expression in pancreatic cancer cells. Thus, FLYWCH1 could have tumour suppressive activities. Future studies are required to elucidate their therapeutic and biomarkers efficacy. Take-home message FLYWCH1 is a newly identified protein could control B-catenin expression which leads tumour suppression. Thus, FLYWCH1 would be a therapeutic target for pancreatic cancer treatment in the future.