ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway

PeerJ

article

Juan Luo¹  Beilei Zeng¹  Chunfang Tao¹  Mengqi Lu¹  Guosheng Ren¹ 

[1] Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University;Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University

关键词: ClpP;    Breast cancer;    Signaling pathway;    Database;    Biological functions;    Clinicopathological characteristics;    TCGA;    Prognosis;    Kaplan Meier-plotter;    Oncogene;   

DOI  :  10.7717/peerj.8754

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundCaseinolytic protease P (ClpP), which is located on the inner mitochondrial membrane, degrades mitochondrial proteins damaged by oxidative stress. The role of ClpP varies among tumor types. However, the expression pattern and biological functions of ClpP in breast cancer (BC) have not yet been investigated.MethodsThe Cancer Genome Atlas (TCGA) and Kaplan Meier-plotter database were used to analyze the expression level of ClpP in BC tissues, relationships with clinicopathological characteristics, and the influence on the prognosis of BC. Protein and mRNA expression levels of ClpP in BC cell lines and tissues were detected by quantitative real-time PCR, western blot and immunohistochemical (IHC) analyses. The colony formation assay, transwell assay and flow cytometric analysis were performed to assess various functions of ClpP. Western blot analysis was also conducted to determine the mechanism of ClpP.ResultsClpP expression was markedly increased in BC cells and tissues. High expression of ClpP was significantly correlated with the T stage, estrogen receptor (ER) expression, and poor recurrence-free survival (RFS) in TCGA and Kaplan Meier-plotter database. ClpP silencing significantly inhibited proliferation, migration, invasion, and promoted apoptosis of BC cells, which resulted in suppression of the Src/PI3K/Akt signaling pathway. The gain-of-function assay confirmed partial these results.

【 授权许可】

CC BY