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Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells
Recently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized non-small cell lung cancer (NSCLC) treatment. However, resistance remains a major obstacle. Anexelekto (AXL) is a member of receptor tyrosine kinases (RTKs) and shares the same downstream signaling...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838623/ https://www.ncbi.nlm.nih.gov/pubmed/27712586 http://dx.doi.org/10.3727/096504016X14648701447814 |
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author | Tian, Yaqiong Zhang, Zengli Miao, Liyun Yang, Zhimin Yang, Jie Wang, Yinhua Qian, Danwen Cai, Hourong Wang, Yongsheng |
author_facet | Tian, Yaqiong Zhang, Zengli Miao, Liyun Yang, Zhimin Yang, Jie Wang, Yinhua Qian, Danwen Cai, Hourong Wang, Yongsheng |
author_sort | Tian, Yaqiong |
collection | PubMed |
description | Recently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized non-small cell lung cancer (NSCLC) treatment. However, resistance remains a major obstacle. Anexelekto (AXL) is a member of receptor tyrosine kinases (RTKs) and shares the same downstream signaling pathways with EGFR, such as PI3K/AKT and MAPK/ERK. AXL overexpression in resistant tumors has been implicated in many previous studies in vitro and in vivo. In this study, we further examined whether expression of AXL and its downstream targets increased in gefitinib-resistant PC9 cells (PC9GR). In addition, we hypothesize that knocking down AXL in PC9GR and overexpressing AXL in PC9 using genetic tools can restore and decrease the sensitivity to gefitinib, respectively. We found that silencing AXL could sensitize the resistance to gefitinib, and the downstream pathways were significantly inhibited. Interestingly, we also discovered that increased AXL expression did promote the resistance, and its downstream targets were activated accordingly. Then 69 NSCLC patients who harbored EGFR mutation were recruited to analyze the expression of AXL and the association between AXL expression and clinical characteristics. We found that 5 of the 69 patients were AXL positive (about 7%), and AXL was related to tumor differentiation and tumor size. In this study, we concluded that the molecular mechanisms of AXL mediated resistance involved in the increased activity of the PI3K/AKT and MAPK/ERK1/2 pathways, and AXL overexpression could promote resistance, but it can be weakened when AXL expression is silenced. |
format | Online Article Text |
id | pubmed-7838623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78386232021-02-16 Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells Tian, Yaqiong Zhang, Zengli Miao, Liyun Yang, Zhimin Yang, Jie Wang, Yinhua Qian, Danwen Cai, Hourong Wang, Yongsheng Oncol Res Article Recently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized non-small cell lung cancer (NSCLC) treatment. However, resistance remains a major obstacle. Anexelekto (AXL) is a member of receptor tyrosine kinases (RTKs) and shares the same downstream signaling pathways with EGFR, such as PI3K/AKT and MAPK/ERK. AXL overexpression in resistant tumors has been implicated in many previous studies in vitro and in vivo. In this study, we further examined whether expression of AXL and its downstream targets increased in gefitinib-resistant PC9 cells (PC9GR). In addition, we hypothesize that knocking down AXL in PC9GR and overexpressing AXL in PC9 using genetic tools can restore and decrease the sensitivity to gefitinib, respectively. We found that silencing AXL could sensitize the resistance to gefitinib, and the downstream pathways were significantly inhibited. Interestingly, we also discovered that increased AXL expression did promote the resistance, and its downstream targets were activated accordingly. Then 69 NSCLC patients who harbored EGFR mutation were recruited to analyze the expression of AXL and the association between AXL expression and clinical characteristics. We found that 5 of the 69 patients were AXL positive (about 7%), and AXL was related to tumor differentiation and tumor size. In this study, we concluded that the molecular mechanisms of AXL mediated resistance involved in the increased activity of the PI3K/AKT and MAPK/ERK1/2 pathways, and AXL overexpression could promote resistance, but it can be weakened when AXL expression is silenced. Cognizant Communication Corporation 2016-09-14 /pmc/articles/PMC7838623/ /pubmed/27712586 http://dx.doi.org/10.3727/096504016X14648701447814 Text en Copyright © 2016 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Tian, Yaqiong Zhang, Zengli Miao, Liyun Yang, Zhimin Yang, Jie Wang, Yinhua Qian, Danwen Cai, Hourong Wang, Yongsheng Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells |
title | Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells |
title_full | Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells |
title_fullStr | Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells |
title_full_unstemmed | Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells |
title_short | Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells |
title_sort | anexelekto (axl) increases resistance to egfr-tki and activation of akt and erk1/2 in non-small cell lung cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838623/ https://www.ncbi.nlm.nih.gov/pubmed/27712586 http://dx.doi.org/10.3727/096504016X14648701447814 |
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