Gastric cancer and role of H.pylori:
H.pylori has two importantvirulence factors.
These both are carcinogenic in nature and these are protein in nature. The proteinVacA is present In All H.pyloriStrains. It induces pore formation and causes apoptosis by interfering with mitochondrial Functions.It also binds to CD4+ T cells and prevent its dephosphorylating. So phosphorylated nuclear factor of activated T cells (NFAT) remains in cytosol and cannot activate T cells proliferation. VacA also inserts Immunosuppressive effects by inducing dendritic cells to produce anti-inflammatorycytokines e.g. IL 10 and IL 18.These activities enhance Gastric tumour survival.(Noto, J. M., & Peek Jr, R. M. 2017).
The Cag is collection of genes that is not present in every Strain of H.pylori
Genes which have CagAPathogenicityencode protein which form type 4 bacterial serotonin system (T4SS).The protein CagA can undergo phosphorylation in Gastric epithelial cells, leading to cell scattering and Elongation.
A host protein namedB catenin which has strong association withcancer development. Beta catenin is downstream component of Wnt transductionpathway. H pylori induces β-catenin activity through injection of CagA into gastric epithelial cells. Inaddition to its cytoplasmic form, β-catenin also exists in a membrane-bound form that linksthe E-cadherin receptor to the actin cytoskeleton. Intracellular CagA interacts with Cadherin, disrupting its association with β-catenin and allowing its translocation into the nucleus. The result of this translocation is the activation of genes involved in gastric cancer, such as caudal type home box 1 (CDX1)38, which encodes an intestine-specific transcription factor that is required for the intestinal metaplasia observed in intestinal type gastricadenocarcinoma(Stewart, O. A., et al 2020)