title: Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation.
abstract: The epithelial-mesenchymal transition (EMT) enhances cellular invasiveness and confers tumor cells with cancer stem cell-like characteristics, through transcriptional and translational mechanisms. The mechanisms maintaining transcriptional and translational repression of EMT and cellular invasion are poorly understood. Herein, the cell fate determination factor Dachshund (DACH1), suppressed EMT via repression of cytoplasmic translational induction of Snail by inactivating the Y box-binding protein (YB-1). In the nucleus, DACH1 antagonized YB-1-mediated oncogenic transcriptional modules governing cell invasion. DACH1 blocked YB-1-induced mammary tumor growth and EMT in mice. In basal-like breast cancer, the reduced expression of DACH1 and increased YB-1 correlated with poor metastasis-free survival. The loss of DACH1 suppression of both cytoplasmic translational and nuclear transcriptional events governing EMT and tumor invasion may contribute to poor prognosis in basal-like forms of breast cancer, a relatively aggressive disease subtype.
authors: Authors' Affiliations: Department of Cancer Biology; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China; and Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, British Columbia, Canada.
authors: Kongming
authors: K
authors: Wu
authors: Ke
authors: K
authors: Chen
authors: Chenguang
authors: C
authors: Wang
authors: Xuanmao
authors: X
authors: Jiao
authors: Liping
authors: L
authors: Wang
authors: Jie
authors: J
authors: Zhou
authors: Jing
authors: J
authors: Wang
authors: Zhiping
authors: Z
authors: Li
authors: Sankar
authors: S
authors: Addya
authors: Poul H
authors: PH
authors: Sorensen
authors: Michael P
authors: MP
authors: Lisanti
authors: Andrew
authors: A
authors: Quong
authors: Adam
authors: A
authors: Ertel
authors: Richard G
authors: RG
authors: Pestell
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C486747:DACH1 protein, human; D005136:Eye Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1