CFTR OVEREXPRESSION MAY CONTRIBUTE TO COLORECTAL CANCER

ALEJANDRA PALMA; MILENI SOARES MACHADO; CECILIA LIRA; FRANCISCO ROSA; FERNANDA RUBIO; GABRIELA MARINO; BASILIO KOTSIAS; MONICA COSTAS

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Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2020; 2020

Sociedad Argentina de Investigación Clínica

CFTR mutations cause not only cystic fibrosis disease, but also increasethe risk of colorectal cancer. However, its probably role incolorectal cancer from patients without cystic fibrosis has not beenpreviously investigated. RAC3 is a nuclear receptor coactivator usuallyoverexpressed in several tumors, required to maintaining thecancer stemness. We investigated the functional relationship betweenCFTR and RAC3 for maintaining cancer stemness in humancolorectal cancer.Previously we investigated cancer stemness using a stable transfectionof shCFTR or shRAC3 in HCT116 cells, and we found thatCFTR downregulation inhibits the cancer stem phenotype. We alsofound that CD133+ side population expresses higher levels of RAC3and CFTR than CD133- and RAC3 overexpression increases CFTRexpression.To further investigate this, we performed bioinformatics analysis inboth human colorectal cancer samples and Caco-2 cells. In order todo these we used two datasets: 1) CD133+ or CD133- side populationsand 2) CFTRwt or CFTRmut cells.First we analyzed the expression levels of CFTR mRNA in colorectalcancer samples from patients without cystic fibrosis using the Xenaplatform (TCGA). The CFTR mRNA without mutations was higherthan the CFTR mRNA with mutations and this correlates with an increasedexpression of RAC3. Then we compared the gene expressionbetween CD133+ cells and CFTRwt cells using different platforms(ConsensusPathDB, STRING, Cytoscape, GeneMANIA). Wefound a common gene expression pattern between them involved ininflammatory and nuclear receptor pathways that contribute to colorectalcancer development.From these and our previous results we conclude that althoughCFTR mutation may increase the risk of colorectal cancer, there areother pathways by which CFTR overexpression may also contributeto this disease, maintaining the cancer stemness and inducing tumordevelopment.