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

BACKGROUND: Caseinolytic 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 ye...

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Autores principales: Luo, Juan, Zeng, Beilei, Tao, Chunfang, Lu, Mengqi, Ren, Guosheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069407/
https://www.ncbi.nlm.nih.gov/pubmed/32195060
http://dx.doi.org/10.7717/peerj.8754
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author Luo, Juan
Zeng, Beilei
Tao, Chunfang
Lu, Mengqi
Ren, Guosheng
author_facet Luo, Juan
Zeng, Beilei
Tao, Chunfang
Lu, Mengqi
Ren, Guosheng
author_sort Luo, Juan
collection PubMed
description BACKGROUND: Caseinolytic 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. METHODS: The 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. RESULTS: ClpP 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.
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spelling pubmed-70694072020-03-19 ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway Luo, Juan Zeng, Beilei Tao, Chunfang Lu, Mengqi Ren, Guosheng PeerJ Cell Biology BACKGROUND: Caseinolytic 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. METHODS: The 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. RESULTS: ClpP 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. PeerJ Inc. 2020-03-10 /pmc/articles/PMC7069407/ /pubmed/32195060 http://dx.doi.org/10.7717/peerj.8754 Text en ©2020 Luo et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Cell Biology
Luo, Juan
Zeng, Beilei
Tao, Chunfang
Lu, Mengqi
Ren, Guosheng
ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway
title ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway
title_full ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway
title_fullStr ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway
title_full_unstemmed ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway
title_short ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway
title_sort clpp regulates breast cancer cell proliferation, invasion and apoptosis by modulating the src/pi3k/akt signaling pathway
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069407/
https://www.ncbi.nlm.nih.gov/pubmed/32195060
http://dx.doi.org/10.7717/peerj.8754
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