The oncogenic role of Streptococcus gallolyticus subsp. Gallolyticus-Phosphoproteome-Part1

ABSTRACT: Streptococcus gallolyticus subsp. gallolyticus (SGG), an opportunistic gram-positive pathogen responsible for septicemia and endocarditis in the elderly, is often associated with colon cancer (CRC). In this work, we investigated the oncogenic role of SGG strain UCN34 using the azoxymethane (AOM)-induced CRC model in vivo, organoids formation ex vivo and full proteomic and phosphoproteomic analysis from murine colons. To identify SGG-specific pathogenic traits, the choice of the control bacterium was important, and we selected the genetically closest and non-pathogenic relative of SGG named S. gallolyticus subsp. macedonicus (SGM). We showed that SGG UCN34 accelerates colon tumor development in the murine CRC model. To test SGG’s capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. To understand the molecular changes induced by SGG UCN34, we compared full proteome and phosphoproteome analysis of murine colon chronically colonized by SGG UCN34 or SGM. We found that 136 proteins and 583 phosphorylation sites were differentially regulated following colonization by SGG UCN34. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift induced specifically with SGG UCN34, as most proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed possible activation by SGG UCN34 of several cancer hallmark pathways, i.e. MAPK (ERK, JNK and p38), mTOR and integrin/ILK/actin signaling. Altogether, our results reveal for the first time that the oncogenic role of SGG UCN34 is associated with activation of multiple cancer-related signaling pathways which cannot be recapitulated in basic in vitro culture models.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Colon

DISEASE(S): Colon Cancer

SUBMITTER: Vanessa Masson  

LAB HEAD: Damarys Loew

PROVIDER: PXD038270 | Pride | 2023-09-22

REPOSITORIES: Pride