Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis.

ABSTRACT: FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers^1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies

SUBMITTER: Pastushenko I 

PROVIDER: S-EPMC7612440 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature