title: Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein.
abstract: TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment.
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.|State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 999078, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Wei
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Jingliang
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Boxv
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Md Asaduzzaman
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: National Center for International Research of Biological Targeting Diagnosis and Therapy &Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research &Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: National Center for International Research of Biological Targeting Diagnosis and Therapy &Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research &Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: National Center for International Research of Biological Targeting Diagnosis and Therapy &Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research &Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, School of Life Sciences &the State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410013, China.
authors.forename: Hanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania 19131, USA.
authors.forename: Dianzheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: National Center for International Research of Biological Targeting Diagnosis and Therapy &Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research &Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Junjiang
authors.initials: J
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D000076183:Tripartite Motif-Containing Protein 28 / Q000235:genetics* / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28