title: DEAR1, a novel tumor suppressor that regulates cell polarity and epithelial plasticity.
abstract: Elucidation of the regulatory controls on epithelial plasticity is pivotal not only to better understand the nature of metastasis but also for the design of targeted therapies to prevent the earliest steps in migration and invasion from the primary tumor. This review will highlight the role of the novel TRIM protein DEAR1 (annotated as TRIM62) in the regulation of apical-basal polarity and acinar morphogenesis as well as its function as a chromosome 1p35 tumor suppressor and negative regulator of TGFβ-driven epithelial-mesenchymal transition (EMT). DEAR1 binds to and promotes the ubiquitination of SMAD3, the major effector of TGFβ-mediated EMT, as well as downregulates SMAD3 targets SNAIL1/2, master transcriptional regulators of EMT. Cumulative results suggest a novel paradigm for DEAR1 in the regulation of the breast tumor microenvironment, polarity, and EMT. Because DEAR1 undergoes loss-of-function mutations, homozygous deletion, as well as copy-number losses in multiple epithelial cancers, including breast cancer, DEAR1 has clinical use as a predictive and prognostic biomarker as well as for stratifying breast cancers and potentially other epithelial tumor types for targeted therapies aimed at the pathways regulated by DEAR1.
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nanyue
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Seetharaman
authors.initials: S
authors.lastname: Balasenthil
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Program in Human and Molecular Genetics, University of Texas Graduate School of Biomedical Sciences, Houston, Texas.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Reuther
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Program in Human and Molecular Genetics, University of Texas Graduate School of Biomedical Sciences, Houston, Texas. akillary@mdanderson.org.
authors.forename: Ann McNeill
authors.initials: AM
authors.lastname: Killary
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016764:Cell Polarity; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins; C583162:TRIM62 protein, human; D044767:Ubiquitin-Protein Ligases