CHD4-mediated loss of E-cadherin determines metastatic ability in triple negative breast cancer cells
CHD4-mediated loss of E-cadherin determines metastatic ability in triple negative breast cancer cells
复制标题
DOI：
10.1016/j.yexcr.2017.12.032
复制
发表时间：
2018-02-15
影响因子：
3.7
通讯作者：
Pan, Mei-Ren
中科院分区：
文献类型：
--
作者：
Luo, Chi-Wen;Wu, Chun-Chieh;Pan, Mei-Ren
三阴性乳腺癌(TNBC)是一种具有侵袭性(复发转移率高)、预后差的肿瘤亚型。因此，研究导致恶性TNBCs的决定因素对于发展个体化治疗和提高生存率是必要的。在这项研究中，我们首先通过免疫组织化学染色分析了60例TNBC患者中嗜铬区域解旋酶DNA结合蛋白4(CHD4)的水平。然后，我们阐明了CHD4在TNBC和非TNBC细胞系中的作用。我们的临床数据表明，CHD4的高表达与转移分期、肿瘤复发和生存状况呈正相关。与临床分析数据一致的是，我们的体外数据还表明，高水平的CHD4与TNBC细胞的恶性行为呈正相关，如细胞运动和死亡率。进一步分析，我们发现E-钙粘蛋白、N-钙粘蛋白和纤维蛋白参与了CHD4介导的上皮-间充质转化(EMT)。CHD4的沉默也增加了顺铂和PARP1抑制剂的药物敏感性，尤其是在TNBC细胞中。总之，我们的研究结果表明，CHD4不仅是一个潜在的预测TNBC患者生存的生物标志物，而且在开发新的TNBC抗癌药物方面也是一个强有力的候选者。
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.