Epiregulin as a therapeutic target in non-small-cell lung cancer

Noriaki Sunaga,1,2 Kyoichi Kaira2,31Oncology Center, Gunma University Hospital, 2Department of Medicine and Molecular Science, 3Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, JapanAbstract: Epiregulin (EREG) belongs to the ErbB family of ligands. ER...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sunaga N, Kaira K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/584722e9cd264212b8c822f59bb017e2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:584722e9cd264212b8c822f59bb017e2
record_format	dspace
spelling	oai:doaj.org-article:584722e9cd264212b8c822f59bb017e22021-12-02T08:29:52ZEpiregulin as a therapeutic target in non-small-cell lung cancer1179-2728https://doaj.org/article/584722e9cd264212b8c822f59bb017e22015-10-01T00:00:00Zhttps://www.dovepress.com/epiregulin-as-a-therapeutic-target-in-non-small-cell-lung-cancer-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Noriaki Sunaga,1,2 Kyoichi Kaira2,31Oncology Center, Gunma University Hospital, 2Department of Medicine and Molecular Science, 3Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, JapanAbstract: Epiregulin (EREG) belongs to the ErbB family of ligands. EREG binds to EGFR and ErbB4 receptor and stimulates homodimers of EGFR and ErbB4 in addition to all possible heterodimeric ErbB complexes, resulting in the activation of downstream signaling pathways. EREG is overexpressed in various human cancers and has been implicated in tumor progression and metastasis. Oncogenic activation of the MEK/ERK pathway plays a central role in the regulation of EREG expression. Non-small-cell lung cancers (NSCLCs) harboring KRAS, BRAF, or EGFR mutations overexpress EREG, and abrogation of such mutations or inhibition of MEK or ERK downregulates the expression of EREG. Elevated EREG expression in NSCLC is associated with aggressive tumor phenotypes and unfavorable prognosis, especially in oncogenic KRAS-driven lung adenocarcinomas. The finding that attenuation of EREG inhibits cell growth and induces apoptosis in KRAS-mutant and EREG-overexpressing NSCLC cell lines suggests that targeting EREG might be a treatment option for KRAS-mutant NSCLC, although further studies are necessary to elucidate its therapeutic value. These observations suggest that oncogenic mutations in the EGFR, KRAS, or BRAF genes induce EREG upregulation through the activation of MEK/ERK pathway in NSCLC cells, whereas overproduced EREG stimulates the EGFR/ErbB receptors and activates multiple downstream signaling pathways, leading to tumor progression and metastasis of these oncogene-driven NSCLCs. This paper reviews the current understanding of the oncogenic role of EREG and highlights its potential as a therapeutic target for NSCLC.Keywords: epiregulin, NSCLC, KRAS mutation, therapeutic targetSunaga NKaira KDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol 2015, Iss default, Pp 91-98 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sunaga N Kaira K Epiregulin as a therapeutic target in non-small-cell lung cancer
description	Noriaki Sunaga,1,2 Kyoichi Kaira2,31Oncology Center, Gunma University Hospital, 2Department of Medicine and Molecular Science, 3Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, JapanAbstract: Epiregulin (EREG) belongs to the ErbB family of ligands. EREG binds to EGFR and ErbB4 receptor and stimulates homodimers of EGFR and ErbB4 in addition to all possible heterodimeric ErbB complexes, resulting in the activation of downstream signaling pathways. EREG is overexpressed in various human cancers and has been implicated in tumor progression and metastasis. Oncogenic activation of the MEK/ERK pathway plays a central role in the regulation of EREG expression. Non-small-cell lung cancers (NSCLCs) harboring KRAS, BRAF, or EGFR mutations overexpress EREG, and abrogation of such mutations or inhibition of MEK or ERK downregulates the expression of EREG. Elevated EREG expression in NSCLC is associated with aggressive tumor phenotypes and unfavorable prognosis, especially in oncogenic KRAS-driven lung adenocarcinomas. The finding that attenuation of EREG inhibits cell growth and induces apoptosis in KRAS-mutant and EREG-overexpressing NSCLC cell lines suggests that targeting EREG might be a treatment option for KRAS-mutant NSCLC, although further studies are necessary to elucidate its therapeutic value. These observations suggest that oncogenic mutations in the EGFR, KRAS, or BRAF genes induce EREG upregulation through the activation of MEK/ERK pathway in NSCLC cells, whereas overproduced EREG stimulates the EGFR/ErbB receptors and activates multiple downstream signaling pathways, leading to tumor progression and metastasis of these oncogene-driven NSCLCs. This paper reviews the current understanding of the oncogenic role of EREG and highlights its potential as a therapeutic target for NSCLC.Keywords: epiregulin, NSCLC, KRAS mutation, therapeutic target
format	article
author	Sunaga N Kaira K
author_facet	Sunaga N Kaira K
author_sort	Sunaga N
title	Epiregulin as a therapeutic target in non-small-cell lung cancer
title_short	Epiregulin as a therapeutic target in non-small-cell lung cancer
title_full	Epiregulin as a therapeutic target in non-small-cell lung cancer
title_fullStr	Epiregulin as a therapeutic target in non-small-cell lung cancer
title_full_unstemmed	Epiregulin as a therapeutic target in non-small-cell lung cancer
title_sort	epiregulin as a therapeutic target in non-small-cell lung cancer
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/584722e9cd264212b8c822f59bb017e2
work_keys_str_mv	AT sunagan epiregulinasatherapeutictargetinnonsmallcelllungcancer AT kairak epiregulinasatherapeutictargetinnonsmallcelllungcancer
_version_	1718398484999045120

Epiregulin as a therapeutic target in non-small-cell lung cancer

Ejemplares similares