AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells

Summary: Neutrophil elastase (NE) promotes multiple stages of tumorigenesis. However, little is known regarding the molecular mechanisms underlying its stimulatory role. This study shows that NE triggers dose-dependent ERK signaling and cell migration in a panel of prostate cell lines representing t...

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Autores principales:	Zhiguang Xiao, Stephen R. Hammes
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cancer Cell biology Science Q
Acceso en línea:	https://doaj.org/article/04603845ad5d458e8807b2348343915f
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spelling	oai:doaj.org-article:04603845ad5d458e8807b2348343915f2021-11-20T05:09:07ZAXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells2589-004210.1016/j.isci.2021.103270https://doaj.org/article/04603845ad5d458e8807b2348343915f2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012396https://doaj.org/toc/2589-0042Summary: Neutrophil elastase (NE) promotes multiple stages of tumorigenesis. However, little is known regarding the molecular mechanisms underlying its stimulatory role. This study shows that NE triggers dose-dependent ERK signaling and cell migration in a panel of prostate cell lines representing the spectrum of prostate cell malignancy. All cell lines tested internalize NE; however, NE endocytosis is not required for ERK activation. Instead, NE acts extracellularly by stimulating the release of amphiregulin to initiate EGFR-dependent signaling. Inhibiting amphiregulin's biological activity with neutralizing antibodies, as well as gene silencing of amphiregulin or EGFR, attenuates NE-induced migration in normal and benign prostatic cells. Alternatively, in prostate cancer cells, knockdown of receptor tyrosine kinase AXL, but not EGFR, impairs both basal and NE-stimulated migration. When prostate cells progress to malignancy, the switch from EGFR-to AXL-dependence in NE-mediated migration implies the potential combined application of EGFR and AXL targeted therapy in prostate cancer treatment.Zhiguang XiaoStephen R. HammesElsevierarticleCancerCell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103270- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cancer Cell biology Science Q
spellingShingle	Cancer Cell biology Science Q Zhiguang Xiao Stephen R. Hammes AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells
description	Summary: Neutrophil elastase (NE) promotes multiple stages of tumorigenesis. However, little is known regarding the molecular mechanisms underlying its stimulatory role. This study shows that NE triggers dose-dependent ERK signaling and cell migration in a panel of prostate cell lines representing the spectrum of prostate cell malignancy. All cell lines tested internalize NE; however, NE endocytosis is not required for ERK activation. Instead, NE acts extracellularly by stimulating the release of amphiregulin to initiate EGFR-dependent signaling. Inhibiting amphiregulin's biological activity with neutralizing antibodies, as well as gene silencing of amphiregulin or EGFR, attenuates NE-induced migration in normal and benign prostatic cells. Alternatively, in prostate cancer cells, knockdown of receptor tyrosine kinase AXL, but not EGFR, impairs both basal and NE-stimulated migration. When prostate cells progress to malignancy, the switch from EGFR-to AXL-dependence in NE-mediated migration implies the potential combined application of EGFR and AXL targeted therapy in prostate cancer treatment.
format	article
author	Zhiguang Xiao Stephen R. Hammes
author_facet	Zhiguang Xiao Stephen R. Hammes
author_sort	Zhiguang Xiao
title	AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells
title_short	AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells
title_full	AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells
title_fullStr	AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells
title_full_unstemmed	AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells
title_sort	axl cooperates with egfr to mediate neutrophil elastase-induced migration of prostate cancer cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/04603845ad5d458e8807b2348343915f
work_keys_str_mv	AT zhiguangxiao axlcooperateswithegfrtomediateneutrophilelastaseinducedmigrationofprostatecancercells AT stephenrhammes axlcooperateswithegfrtomediateneutrophilelastaseinducedmigrationofprostatecancercells
_version_	1718419520905805824

AXL cooperates with EGFR to mediate neutrophil elastase-induced migration of prostate cancer cells

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