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Exp Cell Res. 2018 Feb 1;363(1):65-72. doi: 10.1016/j.yexcr.2017.12.032. Epub 2018 Jan 3.

CHD4-mediated loss of E-cadherin determines metastatic ability in triple-negative breast cancer cells.

Author information

1
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Cardiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
2
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
3
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
4
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
5
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
6
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
7
Division of Colon and Rectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
8
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Municipal Hsiao Kang Hospital, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: mifeho@kmu.edu.tw.
9
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: mrpan@cc.kmu.edu.tw.

Abstract

Triple-negative breast cancer (TNBC) is a subtype of cancer with aggressive behaviors (high recurrence and metastasis rate) and poor prognosis. Therefore, studying the determining factors that lead to malignant TNBCs is necessary to develop personalized therapy and improve survival rates. In this study, we first analyzed levels of chromodomain helicase DNA binding protein 4 (CHD4) in 60 TNBC patients by immunohistochemical staining. We then clarified the role of CHD4 in TNBC and non-TNBC cell lines. Our clinical data indicated that higher CHD4 expression is positively correlated with metastatic stage, tumor recurrence, and survival status. Consistent with the clinical analytical data, our in vitro data also indicated that high level of CHD4 is positively correlated with malignant behaviors in TNBC cells, such as cell motility and mortality. For further analyses, we found that E-cadherin, N-cadherin and fibronetin are involved in CHD4-mediated epithelial-mesenchymal transition (EMT). Silencing of CHD4 also increased drug sensitivity to cisplatin and PARP1 inhibitor, especially in TNBC cells. Altogether, our findings showed that CHD4 is not only a potential prognostic biomarker for TNBC patient survival, but is also a powerful candidate in the development of new anti-cancer agents in TNBC.

KEYWORDS:

CHD4; Cell motility; Drug sensitivity; Triple-negative breast cancer

PMID:
29305962
DOI:
10.1016/j.yexcr.2017.12.032
[Indexed for MEDLINE]

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