FECAL MICROORGANISMS FROM CRC PATIENTS INDUCE THE ACTIVATION OF ONCOGENIC TRANSDUC- TION SIGNAL PATHWAYS

BERNACCHIA JULIANA LOURDES; PALMA, ALEJANDRA GRACIELA; ROSA, FRANCISCO DAMIÁN; LIRA, MARÍA CECILIA; DE PAULIS ADRIANA; MANGIERI NATALIA; BERTONA EUGENIA; FERNANDEZ MELISA; SAMBRESQUI A; LAUDANNO OSCAR; VAZQUEZ LEVIN MÓNICA; RUBIO M. F.; COSTAS M. A.

Congreso; LXVIII ANNUAL MEETING OF SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2023

Although numerous evidence demonstrates the importance of themicrobiome in the development of multiple diseases, such as col-orectal cancer (CRC), mainly due to its immunological action, wehave previously shown that there are signals and pathways thatcould be induced directly by microorganisms in epithelial colorec-tal cells, independent of the immune system, that could probablycontribute to CRC development. The relative abundance of somebacteria shows differences, according to healthy or disease condi-tions. To investigate whether such differences could correlate withdifferent biological effects by direct action over CRC cells, in thiswork we performed experiments of infection of the human colorectalcancer HCT116 cell line with microorganisms from fecal samplesfrom healthy (control) or CRC patients from the IDIM. Firstly, weperformed experiments of cell survival and growth by means of cellstaining with crystal violet and measure of absorbance at 570 nm,after infection by 4 h and incubated during 24 or 48 h with samplesfrom CRC or control patients at multiplicity of infection (MOI) 5, 10or 15 (aerobic plus anaerobic). We found that all the samples inducecell death at 24 h, not more than 50 +/- 10 % for MOI 15. However,the surviving cells continued to proliferate. Through immunofluores-cence (IF) assays at MOI 5, we found that all the samples inducednuclear translocation of NF-κB, β-catenin and the nuclear receptorcoactivator RAC3, which is highly expressed in cancer stem cells aswe previously reported. However, the nuclear localization of β-cat-enin was significantly increased in cells stimulated with samplesfrom CRC compared to control (40 +/- 15%), where an increasedexpression of Vimentin was also observed (p