title: Trim28 contributes to EMT via regulation of E-cadherin and N-cadherin in lung cancer cell lines.
abstract: In previous work, we demonstrated that transcription factor Trim28 (Tripartite motif containing 28) plays a tumor-suppressor role in early-staged adenocarcinoma of the lung due to its ability to restrain transcription of cell cycle-regulating genes. Herein we examine Trim28's role in the epithelial-to-mesenchymal transition (EMT) which is strongly implicated in cancer metastasis. We found that Trim28 plays a role in TGF-β-induced EMT in non-small cell lung cancer cells. Silencing Trim28 with inhibitory RNAs alters the expression of numerous EMT markers, such as E-cadherin and N-cadherin, whereas overexpression of Trim28 has an opposite effect. Trim28 expression is induced following TGF-β treatment at both protein and mRNA levels. Trim28 deficiency impairs TGF-β-induced EMT and decreases cell migration and invasion. Finally, we demonstrate that the expression of Trim28 affects the acetylation and methylation of histones on E-cadherin and N-cadherin promoters. These results suggest that Trim28 contributes to EMT and might be important for tumor metastasis in lung cancer. Taken together with our previous work these results suggest a model in which Trim28 is a tumor suppressor early in the transformation process in lung cancer, but in later stages it functions as an oncogene.
authors.affiliation: Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States of America.
authors.forename: Teresita
authors.initials: T
authors.lastname: Muñoz-Antonia
authors.affiliation: Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States of America.
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Cress
mesh_terms: D014408:Biomarkers, Tumor; D015820:Cadherins / Q000502:physiology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000503:physiopathology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28