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 (BLBC) 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.

Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

“…SUM159 cells were purchased from Asterand and authenticated by the supplier. MDA-MB-231 cells stably transfected with an inducible DACH1 plasmid were a gift from Dr. Richard G. Pestell (Thomas Jefferson University, Philadelphia, PA) (25). MCF-7 and SUM159 cells were transfected with empty pCMV6 (FLAG-tagged) vector or the same vector encoding for FoxQ1 using FuGENE 6.…”

Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling

“…In vitro protein-protein interactions were performed as described previously (24,25). In vitro translated proteins were prepared by coupled transcription-translation with a TNT-coupled reticulocyte lysate kit (Promega) using plasmid DNA (1.0 mg) in a total of 50 mL.…”

Y Box-Binding Protein 1 Promotes Epithelial-Mesenchymal Transition, Invasion, and Metastasis of Cervical Cancer via Enhancing the Expressions of Snail

“…Although it was reported that YB-1 initiates the capindependent translation of Snail mRNAs in breast cancer, 18,19 YB-1Yregulating Snail expression in other tumors including cervical cancer has not yet been investigated. Our experiment showed that the knockdown of endogenous YB-1 in cervical cancer cell lines decreased mRNA and protein levels of Snail but increased mRNA and protein levels of E-cad that is the direct transcriptional suppressive target of Snail and the hall marker of EMT, followed by the decreased invasive potential of the cells.…”

“…Lately, Wu et al 19 reported that DACH1 blocks YB-1Yinduced mammary tumor growth and EMT in mice via repression of cytoplasmic translation of Snail. However, the mode of YB-1 regulation of Snail in other tumors including cervical cancer still needs investigation.…”