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Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC

The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. AD...

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Autores principales: Zhang, Jin-zhi, Liu, Jia, Xu, Yi-xin, Pu, Wang-yang, Shen, Ming-jing, Jiang, Kan-qiu, Yang, Yi-ling, Lu, Jingjing, Deng, Zhengbo, Yang, Yi, Xu, Wei-hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682539/
https://www.ncbi.nlm.nih.gov/pubmed/36439873
http://dx.doi.org/10.7150/ijbs.78354
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author Zhang, Jin-zhi
Liu, Jia
Xu, Yi-xin
Pu, Wang-yang
Shen, Ming-jing
Jiang, Kan-qiu
Yang, Yi-ling
Lu, Jingjing
Deng, Zhengbo
Yang, Yi
Xu, Wei-hua
author_facet Zhang, Jin-zhi
Liu, Jia
Xu, Yi-xin
Pu, Wang-yang
Shen, Ming-jing
Jiang, Kan-qiu
Yang, Yi-ling
Lu, Jingjing
Deng, Zhengbo
Yang, Yi
Xu, Wei-hua
author_sort Zhang, Jin-zhi
collection PubMed
description The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. ADCK2 is overexpressed in local human NSCLC tissues and various primary and established NSCLC cells. In NSCLC cells, ADCK2 shRNA or CRISPR/Cas9 knockout remarkably suppressed cell viability, proliferation, cell cycle progression, cell mobility, and provoked cell apoptosis. Moreover, ADCK2 depletion disrupted mitochondrial functions in NSCLC cells, causing cytochrome C release, mitochondrial depolarization, DNA damage and ATP reduction. Contrarily, ectopic ADCK2 overexpression promoted NSCLC cell growth. Further studies revealed that ADCK2 depletion inactivated Akt-mTOR signaling in primary NSCLC cells. NSCLC xenograft growth in nude mice was significantly hindered after ADCK2 silencing or knockout. ADCK2 depletion, apoptosis induction and oxidative injury as well as ATP reduction and Akt-mTOR inactivation were detected in ADCK2-silenced or ADCK2-knockout NSCLC xenograft tissues. Together overexpressed ADCK2 is important for the growth of NSCLC cells, representing an important therapeutic molecular oncotarget.
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spelling pubmed-96825392022-11-25 Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC Zhang, Jin-zhi Liu, Jia Xu, Yi-xin Pu, Wang-yang Shen, Ming-jing Jiang, Kan-qiu Yang, Yi-ling Lu, Jingjing Deng, Zhengbo Yang, Yi Xu, Wei-hua Int J Biol Sci Research Paper The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. ADCK2 is overexpressed in local human NSCLC tissues and various primary and established NSCLC cells. In NSCLC cells, ADCK2 shRNA or CRISPR/Cas9 knockout remarkably suppressed cell viability, proliferation, cell cycle progression, cell mobility, and provoked cell apoptosis. Moreover, ADCK2 depletion disrupted mitochondrial functions in NSCLC cells, causing cytochrome C release, mitochondrial depolarization, DNA damage and ATP reduction. Contrarily, ectopic ADCK2 overexpression promoted NSCLC cell growth. Further studies revealed that ADCK2 depletion inactivated Akt-mTOR signaling in primary NSCLC cells. NSCLC xenograft growth in nude mice was significantly hindered after ADCK2 silencing or knockout. ADCK2 depletion, apoptosis induction and oxidative injury as well as ATP reduction and Akt-mTOR inactivation were detected in ADCK2-silenced or ADCK2-knockout NSCLC xenograft tissues. Together overexpressed ADCK2 is important for the growth of NSCLC cells, representing an important therapeutic molecular oncotarget. Ivyspring International Publisher 2022-10-24 /pmc/articles/PMC9682539/ /pubmed/36439873 http://dx.doi.org/10.7150/ijbs.78354 Text en © The author(s) 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/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhang, Jin-zhi
Liu, Jia
Xu, Yi-xin
Pu, Wang-yang
Shen, Ming-jing
Jiang, Kan-qiu
Yang, Yi-ling
Lu, Jingjing
Deng, Zhengbo
Yang, Yi
Xu, Wei-hua
Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC
title Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC
title_full Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC
title_fullStr Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC
title_full_unstemmed Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC
title_short Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC
title_sort identification of the mitochondrial protein adck2 as a therapeutic oncotarget of nsclc
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682539/
https://www.ncbi.nlm.nih.gov/pubmed/36439873
http://dx.doi.org/10.7150/ijbs.78354
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