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Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway

BACKGROUND: Drug resistance is common in cancer chemotherapy. This study investigates the role of Glycerol kinase 5 (GK5) in mediating gefitinib resistance in NSCLC. METHODS: The exosomal mRNA of GK5 was detected using a tethered cationic lipoplex nanoparticle (TCLN) biochip. Real-time PCR and Weste...

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Autores principales: Zhou, Jian, Qu, Guimei, Zhang, Ge, Wu, Zuoren, Liu, Jing, Yang, Dawei, Li, Jing, Chang, Meijia, Zeng, Hengshan, Hu, Jie, Fang, Tao, Song, Yuanlin, Bai, Chunxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385389/
https://www.ncbi.nlm.nih.gov/pubmed/30791926
http://dx.doi.org/10.1186/s13046-019-1057-7
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author Zhou, Jian
Qu, Guimei
Zhang, Ge
Wu, Zuoren
Liu, Jing
Yang, Dawei
Li, Jing
Chang, Meijia
Zeng, Hengshan
Hu, Jie
Fang, Tao
Song, Yuanlin
Bai, Chunxue
author_facet Zhou, Jian
Qu, Guimei
Zhang, Ge
Wu, Zuoren
Liu, Jing
Yang, Dawei
Li, Jing
Chang, Meijia
Zeng, Hengshan
Hu, Jie
Fang, Tao
Song, Yuanlin
Bai, Chunxue
author_sort Zhou, Jian
collection PubMed
description BACKGROUND: Drug resistance is common in cancer chemotherapy. This study investigates the role of Glycerol kinase 5 (GK5) in mediating gefitinib resistance in NSCLC. METHODS: The exosomal mRNA of GK5 was detected using a tethered cationic lipoplex nanoparticle (TCLN) biochip. Real-time PCR and Western blot were used to examine the expression of GK5 mRNA and protein in gefitinib-sensitive and -resistant human lung adenocarcinoma cells. The cell counting kit-8, EdU assay, flow cytometry, and JC-1 dye were used to measure cell proliferation, cell cycle, and the mitochondrial membrane potential. RESULTS: We found that the exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma was significantly higher compared with that of gefitinib-sensitive patients. The mRNA and protein levels of GK5 were significantly upregulated in gefitinib-resistant human lung adenocarcinoma PC9R and H1975 cells compared with gefitinib-sensitive PC9 cells. Silencing GK5 in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway. CONCLUSIONS: We demonstrated that GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest. GK5 could be a novel therapeutic target for treatment of NSCLC with resistance to EGFR tyrosine kinase inhibitors.
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spelling pubmed-63853892019-03-01 Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway Zhou, Jian Qu, Guimei Zhang, Ge Wu, Zuoren Liu, Jing Yang, Dawei Li, Jing Chang, Meijia Zeng, Hengshan Hu, Jie Fang, Tao Song, Yuanlin Bai, Chunxue J Exp Clin Cancer Res Research BACKGROUND: Drug resistance is common in cancer chemotherapy. This study investigates the role of Glycerol kinase 5 (GK5) in mediating gefitinib resistance in NSCLC. METHODS: The exosomal mRNA of GK5 was detected using a tethered cationic lipoplex nanoparticle (TCLN) biochip. Real-time PCR and Western blot were used to examine the expression of GK5 mRNA and protein in gefitinib-sensitive and -resistant human lung adenocarcinoma cells. The cell counting kit-8, EdU assay, flow cytometry, and JC-1 dye were used to measure cell proliferation, cell cycle, and the mitochondrial membrane potential. RESULTS: We found that the exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma was significantly higher compared with that of gefitinib-sensitive patients. The mRNA and protein levels of GK5 were significantly upregulated in gefitinib-resistant human lung adenocarcinoma PC9R and H1975 cells compared with gefitinib-sensitive PC9 cells. Silencing GK5 in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway. CONCLUSIONS: We demonstrated that GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest. GK5 could be a novel therapeutic target for treatment of NSCLC with resistance to EGFR tyrosine kinase inhibitors. BioMed Central 2019-02-21 /pmc/articles/PMC6385389/ /pubmed/30791926 http://dx.doi.org/10.1186/s13046-019-1057-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhou, Jian
Qu, Guimei
Zhang, Ge
Wu, Zuoren
Liu, Jing
Yang, Dawei
Li, Jing
Chang, Meijia
Zeng, Hengshan
Hu, Jie
Fang, Tao
Song, Yuanlin
Bai, Chunxue
Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway
title Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway
title_full Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway
title_fullStr Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway
title_full_unstemmed Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway
title_short Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway
title_sort glycerol kinase 5 confers gefitinib resistance through srebp1/scd1 signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385389/
https://www.ncbi.nlm.nih.gov/pubmed/30791926
http://dx.doi.org/10.1186/s13046-019-1057-7
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