Targeting G-quadruplex by TMPyP4 for inhibition of colorectal cancer through cell cycle arrest and boosting anti-tumor immunity.

ABSTRACT: G-quadruplex (G4) is a noncanonical DNA secondary structure known to induce DNA damage and regulate the expression of immune-related genes. We aim to exploit the G4 folding as a treatment strategy to trigger anti-tumor immune response. In this study, we observe that the abundant genomic G4 in epithelial cells coexists with increased infiltration of CD8⁺ T cells in colorectal cancer tissue. Furthermore, our data substantiate the inhibitory effect of the G4 ligand TMPyP4 on cancer progression while concurrently stimulating anti-tumor immunity. Mechanistically, TMPyP4 impedes cancer cell proliferation and induces G2/M cell cycle arrest. Additionally, in vivo experiments demonstrate that TMPyP4 enhances the anti-tumor immune response by triggering DNA damage and activating the cGAS-

SUBMITTER: Li P 

PROVIDER: S-EPMC11554887 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature