ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί

(1) Background: Mutations in epidermal growth factor receptor (EGFR) proteins account for many non-small cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors (TKIs) are being used as targeted therapeutics. However, resistance to TKIs continues to increase owing to additional mutations in...

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Autores principales:	Jeon-Soo Lee, Young Eun Choi, Sunshin Kim, Ji-Youn Han, Sung-Ho Goh
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ELF3 non-small cell lung cancer EGFR EGFR-TKI resistance PKCί auranofin Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/efd73dcc6d8f45e9ab8e60d396186314
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spelling	oai:doaj.org-article:efd73dcc6d8f45e9ab8e60d3961863142021-11-25T17:55:03ZELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί10.3390/ijms2222122871422-00671661-6596https://doaj.org/article/efd73dcc6d8f45e9ab8e60d3961863142021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12287https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067(1) Background: Mutations in epidermal growth factor receptor (EGFR) proteins account for many non-small cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors (TKIs) are being used as targeted therapeutics. However, resistance to TKIs continues to increase owing to additional mutations in more than half of the patients receiving EGFR TKI therapy. In addition to targeting new mutations with next-generation therapeutics, it is necessary to find an alternative target to overcome the challenges associated with resistance. (2) Methods: To identify potential alternative targets in patients with NSCLC undergoing targeted therapy, putative targets were identified by transcriptome profiling and validated for their biological and therapeutic effects in vitro and in vivo. (3) Results: ELF3 was found to be differentially expressed in NSCLC, and ELF3 knockdown significantly increased cell death in K-Ras mutant as well as in EGFR L858R/T790M mutation harboring lung cancer cells. We also found that auranofin, an inhibitor of protein kinase C iota (PKCί), a protein upstream of ELF3, effectively induced cell death. (4) Conclusions: Our study suggests that blocking ELF3 is an effective way to induce cell death in NSCLC with K-Ras and EGFR T790M/L858R mutations and thus advocates the use of auranofin as an effective alternative drug to overcome EGFR TKI resistance.Jeon-Soo LeeYoung Eun ChoiSunshin KimJi-Youn HanSung-Ho GohMDPI AGarticleELF3non-small cell lung cancerEGFREGFR-TKI resistancePKCίauranofinBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12287, p 12287 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ELF3 non-small cell lung cancer EGFR EGFR-TKI resistance PKCί auranofin Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ELF3 non-small cell lung cancer EGFR EGFR-TKI resistance PKCί auranofin Biology (General) QH301-705.5 Chemistry QD1-999 Jeon-Soo Lee Young Eun Choi Sunshin Kim Ji-Youn Han Sung-Ho Goh ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
description	(1) Background: Mutations in epidermal growth factor receptor (EGFR) proteins account for many non-small cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors (TKIs) are being used as targeted therapeutics. However, resistance to TKIs continues to increase owing to additional mutations in more than half of the patients receiving EGFR TKI therapy. In addition to targeting new mutations with next-generation therapeutics, it is necessary to find an alternative target to overcome the challenges associated with resistance. (2) Methods: To identify potential alternative targets in patients with NSCLC undergoing targeted therapy, putative targets were identified by transcriptome profiling and validated for their biological and therapeutic effects in vitro and in vivo. (3) Results: ELF3 was found to be differentially expressed in NSCLC, and ELF3 knockdown significantly increased cell death in K-Ras mutant as well as in EGFR L858R/T790M mutation harboring lung cancer cells. We also found that auranofin, an inhibitor of protein kinase C iota (PKCί), a protein upstream of ELF3, effectively induced cell death. (4) Conclusions: Our study suggests that blocking ELF3 is an effective way to induce cell death in NSCLC with K-Ras and EGFR T790M/L858R mutations and thus advocates the use of auranofin as an effective alternative drug to overcome EGFR TKI resistance.
format	article
author	Jeon-Soo Lee Young Eun Choi Sunshin Kim Ji-Youn Han Sung-Ho Goh
author_facet	Jeon-Soo Lee Young Eun Choi Sunshin Kim Ji-Youn Han Sung-Ho Goh
author_sort	Jeon-Soo Lee
title	ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
title_short	ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
title_full	ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
title_fullStr	ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
title_full_unstemmed	ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
title_sort	elf3 is a target that promotes therapeutic efficiency in egfr tyrosine kinase inhibitor-resistant non-small cell lung cancer cells via inhibiting pkcί
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/efd73dcc6d8f45e9ab8e60d396186314
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ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί

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