C1Q⁺ TPP1⁺ macrophages promote colon cancer progression through SETD8-driven p53 methylation.

ABSTRACT:

Background

In many tumors, the tumor suppressor TP53 is not mutated, but functionally inactivated. However, mechanisms underlying p53 functional inactivation remain poorly understood. SETD8 is the sole enzyme known to mono-methylate p53 on lysine 382 (p53^K382me1), resulting in the inhibition of its pro-apoptotic and growth-arresting functions.

Methods

We analyzed SETD8 and p53^K382me1 expression in clinical colorectal cancer (CRC) and inflammatory bowel disease (IBD) samples. Histopathological examinations, RNA sequencing, ChIP assay and preclinical in vivo CRC models, were used to assess the functional role of p53 inactivation in tumor cells and immune cell infiltration.

Results

By integrating bulk RNAseq and scRNAseq approaches in CRC patients,

SUBMITTER: Veschi V 

PROVIDER: S-EPMC11956498 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature