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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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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. |
format | Online Article Text |
id | pubmed-6385389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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