Chloride channel CFTR is associated to cancer stem cells

SOARES MACHADO, MILENI; RUBIO, MARÍA FERNANDA; PALMA, ALEJANDRA; ROSA, FRANCISCO D; COSTAS, MÓNICA ALEJANDRA; MARINO, GABRIELA INÉS; LIRA, MARÍA CECILIA

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

The cancer stem cells (CSC), responsible of tumorigenesis, secondaryfocus formation in metastasis and chemoresistance. We havepreviously demonstrated that while the NF-κB coactivator RAC3 isrequired to maintain the CSC and increase the chemoresistance incolorectal cancer, the NF-κB target gene, cystic fibrosis transmembraneconductance regulator CFTR exerts an anti-apoptotic role.The aim of this work was to determine if CFTR is expressed in humancolorectal cancer cell lines and if this is mainly associated toCSC.We found that it is expressed in the human colorectal HCT116 cells,as determined by RT-PCR and western blot.When we performed the analysis of CFTR expression from publicrepository microarrays data of the human colon cancer cell linesHT29 and CACO-2, we found that the CFTR expression was higherin colonospheres (CSC enriched) from primary HT29 than in cellsgrowing as monolayers and significantly higher in CD133+ (CSC enriched)than in CD133- CACO-2 cells (6 arrays, including 3 CD133+replicates and 3 CD133- replicates; expression values: 2470,30 ±396,13 vs. 582,05 ± 25,73 respectively; p < 0,01).The functional associations among CFTR and RAC3 were analyzedusing Cytoscape and we found that one of the genes in this networkwas Vimentin, a typical mesenchymal marker that we previouslydemonstrated as upregulated by RAC3 overexpression. The analysisof this network by gProfiler software, showed the associationto cell differentiation and maturation processes for CFTR and someof these genes.We conclude that while the CFTR/RAC3 relation type remains to bedetermined, the high CFTR expression could be mainly associatedto CSC in human colorectal cancer.