Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.

ABSTRACT: SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features. A mouse model engineered for Kras^G12D expression in the adult oral epithelium induced benign papillomas, however the combination of Kras^G12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examinat

SUBMITTER: Yang J 

PROVIDER: S-EPMC11300146 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature