Cargando…

S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide

S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its...

Descripción completa

Detalles Bibliográficos
Autores principales: Stewart, Rachel L., Carpenter, Brittany L., West, Dava S., Knifley, Teresa, Liu, Lili, Wang, Chi, Weiss, Heidi L., Gal, Tamas S., Durbin, Eric B., Arnold, Susanne M., O'Connor, Kathleen L., Chen, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085181/
https://www.ncbi.nlm.nih.gov/pubmed/27127879
http://dx.doi.org/10.18632/oncotarget.8969
_version_ 1782463522661203968
author Stewart, Rachel L.
Carpenter, Brittany L.
West, Dava S.
Knifley, Teresa
Liu, Lili
Wang, Chi
Weiss, Heidi L.
Gal, Tamas S.
Durbin, Eric B.
Arnold, Susanne M.
O'Connor, Kathleen L.
Chen, Min
author_facet Stewart, Rachel L.
Carpenter, Brittany L.
West, Dava S.
Knifley, Teresa
Liu, Lili
Wang, Chi
Weiss, Heidi L.
Gal, Tamas S.
Durbin, Eric B.
Arnold, Susanne M.
O'Connor, Kathleen L.
Chen, Min
author_sort Stewart, Rachel L.
collection PubMed
description S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular invasion and decreased overall survival. In addition, depletion of S100A4 by shRNA inhibits NF-κB activity and decreases TNFα-induced MMP9 expression. Furthermore, inhibition of the NF-κB/MMP9 axis decreases lung carcinoma invasive potential. Niclosamide, a reported inhibitor of S100A4, blocks expression and function of S100A4 with a reduction in proliferation, invasion and NF-κB-mediated MMP9 expression. Collectively, this study highlights the importance of the S100A4/NF-κB/MMP9 axis in lung cancer invasion and provides a rationale for targeting S100A4 to combat lung cancer.
format Online
Article
Text
id pubmed-5085181
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-50851812016-10-31 S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide Stewart, Rachel L. Carpenter, Brittany L. West, Dava S. Knifley, Teresa Liu, Lili Wang, Chi Weiss, Heidi L. Gal, Tamas S. Durbin, Eric B. Arnold, Susanne M. O'Connor, Kathleen L. Chen, Min Oncotarget Research Paper S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular invasion and decreased overall survival. In addition, depletion of S100A4 by shRNA inhibits NF-κB activity and decreases TNFα-induced MMP9 expression. Furthermore, inhibition of the NF-κB/MMP9 axis decreases lung carcinoma invasive potential. Niclosamide, a reported inhibitor of S100A4, blocks expression and function of S100A4 with a reduction in proliferation, invasion and NF-κB-mediated MMP9 expression. Collectively, this study highlights the importance of the S100A4/NF-κB/MMP9 axis in lung cancer invasion and provides a rationale for targeting S100A4 to combat lung cancer. Impact Journals LLC 2016-04-25 /pmc/articles/PMC5085181/ /pubmed/27127879 http://dx.doi.org/10.18632/oncotarget.8969 Text en Copyright: © 2016 Stewart et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Stewart, Rachel L.
Carpenter, Brittany L.
West, Dava S.
Knifley, Teresa
Liu, Lili
Wang, Chi
Weiss, Heidi L.
Gal, Tamas S.
Durbin, Eric B.
Arnold, Susanne M.
O'Connor, Kathleen L.
Chen, Min
S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide
title S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide
title_full S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide
title_fullStr S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide
title_full_unstemmed S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide
title_short S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide
title_sort s100a4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the fda-approved anti-helminthic agent niclosamide
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085181/
https://www.ncbi.nlm.nih.gov/pubmed/27127879
http://dx.doi.org/10.18632/oncotarget.8969
work_keys_str_mv AT stewartrachell s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT carpenterbrittanyl s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT westdavas s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT knifleyteresa s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT liulili s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT wangchi s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT weissheidil s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT galtamass s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT durbinericb s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT arnoldsusannem s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT oconnorkathleenl s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide
AT chenmin s100a4drivesnonsmallcelllungcancerinvasionassociateswithpoorprognosisandiseffectivelytargetedbythefdaapprovedantihelminthicagentniclosamide