SMAD4 mutation drives gut microbiome shifts toward tumor progression in colorectal cancer.

ABSTRACT:

Background

Colorectal cancer (CRC) progression is driven by a series of sequential mutations in key driver genes; however, the factors underlying tumor progression and metastasis remain poorly understood. Mutations in TP53 and SMAD4, in particular, are associated with CRC progression. Although gut microbiome dysbiosis is implicated in CRC initiation and progression, the interactions between the microbiome and specific CRC driver mutations, especially those promoting metastasis, are not well defined.

Methods

In this study, we utilized triple mutant (Apc, Kras, Tp53; AKP) and quadruple mutant (Apc, Kras, Tp53, Smad4; AKPS) organoid-based orthotopic mouse models of CRC to investigate the impact of the SMAD4 mutation on microbiome composition.

Results

Our results reveal s

SUBMITTER: Gates TJ 

PROVIDER: S-EPMC12511496 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature