DACH1 inhibits SNAI1-mediated epithelial-mesenchymal transition and represses breast carcinoma metastasis

Oncogenesis
F ZhaoH Wu

Abstract

Epithelial-mesenchymal transition (EMT) has a major role in cancer progression and metastasis. However, the specific mechanism of transcriptional repression involved in this process remains largely unknown. Dachshund homologue 1 (DACH1) expression is lost in invasive breast cancer with poor prognosis, and the role of DACH1 in regulating breast cancer metastasis is poorly understood. In this study, significant correlation between the expression of DACH1 and the morphology of breast cancer cells was observed. Subsequent investigation into the relationship between DACH1 and EMT showed that overexpression of DACH1 in ZR-75-30 cells induced a shift towards epithelial morphology and cell-cell adhesion, as well as increased the expression of the epithelial marker E-cadherin and suppressed cell migration and invasion. In contrast, silencing DACH1 in MCF-7 and T47D cells disrupted the epithelial morphology and cell-cell contact, reduced the expression of E-cadherin, and induced cell migration and invasion. DACH1 also specifically interacted with SNAI1, but not SNAI2, to form a complex, which could bind to the E-box on the E-cadherin promoter in an SNAI1-dependent manner. DACH1 inhibited the transcriptional activity of SNAI1, leading to ...Continue Reading

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Citations

Jan 6, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhe LiuYuanhong Xu
Nov 19, 2015·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Li ZhangFeng-Gang Xiang
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Aug 6, 2020·Molecular Carcinogenesis·Su-Hyeong KimShivendra V Singh
Dec 21, 2016·Breast Cancer Research : BCR·Natsue UehiroMasakazu Toi
Sep 29, 2018·Head & Face Medicine·Jiarui ZhangMing Liu
Jun 19, 2020·Experimental Hematology & Oncology·Bing DongKongming Wu
Jul 1, 2017·Scientific Reports·Hanxiao XuKongming Wu
Jan 7, 2017·Molecular Cancer Research : MCR·Kefeng WangXiaonan Chen

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Methods Mentioned

BETA
two-hybrid
pulldown
ChIP
CoIP
transfection
immunoprecipitation
PCR
Pull-Down

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