4.6 Article

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

Journal

FRONTIERS IN ONCOLOGY
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2019.00262

Keywords

breast cancer; DEPDC1; TCGA; proliferation; PI3K/AKT/mTOR; GSEA

Categories

Funding

  1. Shandong Provincial Natural Science Foundation [ZR2017PH047, ZR2016HL26]
  2. National Natural Science Foundation of the People's Republic of China [81671416]
  3. Yantai Science and Technology Plan [2016WS013]
  4. Research Fundation of Yantai Yuhuangding Hospital [201604]

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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.

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