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DEPDC1的高表达促进乳腺癌细胞的恶性表型并预示乳腺癌患者的不良预后。

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer.

作者信息

Zhao Huishan, Yu Mingwei, Sui Laijian, Gong Benjiao, Zhou Bo, Chen Jian, Gong Zhaohua, Hao Cuifang

机构信息

Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

Department of Orthopedics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

出版信息

Front Oncol. 2019 Apr 12;9:262. doi: 10.3389/fonc.2019.00262. eCollection 2019.

Abstract

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. 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.

摘要

含DEP结构域蛋白1(DEPDC1)是一种新型肿瘤相关基因,在多种癌症中异常表达,参与肿瘤发生和癌症进展。在此,我们研究了DEPDC1在乳腺癌中的功能作用及潜在机制。在本研究中,免疫组织化学结果表明,与配对的相邻正常乳腺组织相比,DEPDC1在乳腺癌组织中高表达,其蛋白水平趋势与来自TCGA数据的mRNA水平一致。此外,DEPDC1 mRNA水平显示与乳腺癌的不良预后和发展关联最强。实验表明,DEPDC1过表达通过调节MCF-7细胞的细胞周期显著促进增殖,而在DEPDC1缺失的MDA-MB-231细胞中发现相反的效果。值得注意的是,进一步研究表明DEPDC1具有促进乳腺癌细胞迁移和侵袭的能力。此外,我们发现DEPDC1导致乳腺癌细胞中PI3K/AKT/mTOR信号通路过度激活。因此,乳腺癌中DEPDC1表达增加与疾病进展和不良生存相关,这表明DEPDC1可能是针对该疾病的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa31/6473048/b6f89fd7a4bf/fonc-09-00262-g0001.jpg

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