DEAR1 is a chromosome 1p35 tumor suppressor and master regulator of TGF-β-driven epithelial-mesenchymal transition.

ABSTRACT:

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Deletion of chromosome 1p35 is a common event in epithelial malignancies. We report that DEAR1 (annotated as TRIM62) is a chromosome 1p35 tumor suppressor that undergoes mutation, copy number variation, and loss of expression in human tumors. Targeted disruption in the mouse recapitulates this human tumor spectrum, with both Dear1(-/-) and Dear1(+/-) mice developing primarily epithelial adenocarcinomas and lymphoma with evidence of metastasis in a subset of mice. DEAR1 loss of function in the presence of TGF-β results in failure of acinar morphogenesis, upregulation of epithelial-mesenchymal transition (EMT) markers, anoikis resistance, migration, and invasion. Furthermore, DEAR1 blocks TGF-β-SMAD3 signaling, resulting in decreased nuclear phosphorylated SMAD3 by binding

SUBMITTER: Chen N 

PROVIDER: S-EPMC4107927 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature