High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer
High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer
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DEPDC1的高表达促进乳腺癌细胞的恶性表型并预测乳腺癌患者的不良预后
DOI：
10.3389/fonc.2019.00262
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发表时间：
2019-04-12
影响因子：
4.7
通讯作者：
Hao, Cuifang
中科院分区：
文献类型：
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作者：
Zhao, Huishan;Yu, Mingwei;Hao, Cuifang
DEPDC 1是一种新型肿瘤相关基因，在多种类型的癌症中异常表达，参与肿瘤的发生和进展。在这里，我们研究了DEPDC 1在乳腺癌中的功能参与和潜在机制。在本研究中，免疫组化结果表明DEPDC 1在乳腺癌组织中的表达高于配对的正常乳腺组织，其在蛋白水平上的趋势与TCGA数据的mRNA水平一致。此外，DEPDC 1 mRNA水平与乳腺癌的不良预后和发展相关性最强。体外实验表明，DEPDC 1过表达可通过调节细胞周期而显著促进MCF-7细胞的增殖，而DEPDC 1缺失的MDA-MB-231细胞则相反。值得注意的是，进一步的研究表明DEPDC 1具有促进乳腺癌细胞迁移和侵袭的能力。此外，我们发现DEPDC 1在乳腺癌细胞中引起PI 3 K/AKT/mTOR信号的过度激活。因此，DEPDC 1在乳腺癌中的表达增加与疾病进展和不良生存相关，这表明DEPDC 1可能是针对该疾病的潜在治疗靶点。
DEP domain containing 1 (DEPDC1) is a novel tumor-associated gene, which is aberrantly expressed in multiple types of cancer and involves in tumorigenesis and cancer progression. Here, we examined the functional involvement and underlying mechanism of DEPDC1 in breast cancer. In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation indicated DEPDC1's ability of promoting breast cancer cells migration and invasion. In addition, we discovered that DEPDC1 caused hyper-activation of PI3K/AKT/mTOR signaling in breast cancer cells. Therefore, the increased DEPDC1 expression in breast cancer is correlated with disease progression and poor survival, which suggested that DEPDC1 might be a potential therapeutic target against this disease.