Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness

Autores
Sahores, A.; Carozzo, A.; May, M.; Gómez, N.; Di Siervi, N.; De Sousa Serro, M.; Yaneff, A.; Rodríguez González, A.; Abba, Martín Carlos; Shayo, C.; Davio, C.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Recent fndings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the signifcance of MRP4 protein levels and function in PDAC progression is still unclear. The aim of this study was to determine the role of MRP4 in PDAC tumor aggressiveness. Bioinformatic studies revealed that PDAC samples show higher MRP4 transcript levels compared to normal adjacent pancreatic tissue and circulating tumor cells express higher levels of MRP4 than primary tumors. Also, high levels of MRP4 are typical of high-grade PDAC cell lines and associate with an epithelial-mesenchymal phenotype. Moreover, PDAC patients with high levels of MRP4 depict dysregulation of pathways associated with migration, chemotaxis and cell adhesion. Silencing MRP4 in PANC1 cells reduced tumorigenicity and tumor growth and impaired cell migration. Transcriptomic analysis revealed that MRP4 silencing alters PANC1 gene expression, mainly dysregulating pathways related to cell-to-cell interactions and focal adhesion. Contrarily, MRP4 overexpression signifcantly increased BxPC-3 growth rate, produced a switch in the expression of EMT markers, and enhanced experimental metastatic incidence. Altogether, our results indicate that MRP4 is associated with a more aggressive phenotype in PDAC, boosting pancreatic tumorigenesis and metastatic capacity, which could fnally determine a fast tumor progression in PDAC patients.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Materia
Medicina
cancer
pancreatic cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/107878
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/107878
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressivenessSahores, A.Carozzo, A.May, M.Gómez, N.Di Siervi, N.De Sousa Serro, M.Yaneff, A.Rodríguez González, A.Abba, Martín CarlosShayo, C.Davio, C.Medicinacancerpancreatic cancerRecent fndings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the signifcance of MRP4 protein levels and function in PDAC progression is still unclear. The aim of this study was to determine the role of MRP4 in PDAC tumor aggressiveness. Bioinformatic studies revealed that PDAC samples show higher MRP4 transcript levels compared to normal adjacent pancreatic tissue and circulating tumor cells express higher levels of MRP4 than primary tumors. Also, high levels of MRP4 are typical of high-grade PDAC cell lines and associate with an epithelial-mesenchymal phenotype. Moreover, PDAC patients with high levels of MRP4 depict dysregulation of pathways associated with migration, chemotaxis and cell adhesion. Silencing MRP4 in PANC1 cells reduced tumorigenicity and tumor growth and impaired cell migration. Transcriptomic analysis revealed that MRP4 silencing alters PANC1 gene expression, mainly dysregulating pathways related to cell-to-cell interactions and focal adhesion. Contrarily, MRP4 overexpression signifcantly increased BxPC-3 growth rate, produced a switch in the expression of EMT markers, and enhanced experimental metastatic incidence. Altogether, our results indicate that MRP4 is associated with a more aggressive phenotype in PDAC, boosting pancreatic tumorigenesis and metastatic capacity, which could fnally determine a fast tumor progression in PDAC patients.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicadas2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/107878enginfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7450045&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-020-71181-winfo:eu-repo/semantics/altIdentifier/issn/2045-2322info:eu-repo/semantics/altIdentifier/pmid/32848164info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-71181-winfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:56:06Zoai:sedici.unlp.edu.ar:10915/107878Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:56:06.762SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
title Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
spellingShingle Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
Sahores, A.
Medicina
cancer
pancreatic cancer
title_short Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
title_full Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
title_fullStr Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
title_full_unstemmed Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
title_sort Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
dc.creator.none.fl_str_mv Sahores, A.
Carozzo, A.
May, M.
Gómez, N.
Di Siervi, N.
De Sousa Serro, M.
Yaneff, A.
Rodríguez González, A.
Abba, Martín Carlos
Shayo, C.
Davio, C.
author Sahores, A.
author_facet Sahores, A.
Carozzo, A.
May, M.
Gómez, N.
Di Siervi, N.
De Sousa Serro, M.
Yaneff, A.
Rodríguez González, A.
Abba, Martín Carlos
Shayo, C.
Davio, C.
author_role author
author2 Carozzo, A.
May, M.
Gómez, N.
Di Siervi, N.
De Sousa Serro, M.
Yaneff, A.
Rodríguez González, A.
Abba, Martín Carlos
Shayo, C.
Davio, C.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Medicina
cancer
pancreatic cancer
topic Medicina
cancer
pancreatic cancer
dc.description.none.fl_txt_mv Recent fndings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the signifcance of MRP4 protein levels and function in PDAC progression is still unclear. The aim of this study was to determine the role of MRP4 in PDAC tumor aggressiveness. Bioinformatic studies revealed that PDAC samples show higher MRP4 transcript levels compared to normal adjacent pancreatic tissue and circulating tumor cells express higher levels of MRP4 than primary tumors. Also, high levels of MRP4 are typical of high-grade PDAC cell lines and associate with an epithelial-mesenchymal phenotype. Moreover, PDAC patients with high levels of MRP4 depict dysregulation of pathways associated with migration, chemotaxis and cell adhesion. Silencing MRP4 in PANC1 cells reduced tumorigenicity and tumor growth and impaired cell migration. Transcriptomic analysis revealed that MRP4 silencing alters PANC1 gene expression, mainly dysregulating pathways related to cell-to-cell interactions and focal adhesion. Contrarily, MRP4 overexpression signifcantly increased BxPC-3 growth rate, produced a switch in the expression of EMT markers, and enhanced experimental metastatic incidence. Altogether, our results indicate that MRP4 is associated with a more aggressive phenotype in PDAC, boosting pancreatic tumorigenesis and metastatic capacity, which could fnally determine a fast tumor progression in PDAC patients.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
description Recent fndings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the signifcance of MRP4 protein levels and function in PDAC progression is still unclear. The aim of this study was to determine the role of MRP4 in PDAC tumor aggressiveness. Bioinformatic studies revealed that PDAC samples show higher MRP4 transcript levels compared to normal adjacent pancreatic tissue and circulating tumor cells express higher levels of MRP4 than primary tumors. Also, high levels of MRP4 are typical of high-grade PDAC cell lines and associate with an epithelial-mesenchymal phenotype. Moreover, PDAC patients with high levels of MRP4 depict dysregulation of pathways associated with migration, chemotaxis and cell adhesion. Silencing MRP4 in PANC1 cells reduced tumorigenicity and tumor growth and impaired cell migration. Transcriptomic analysis revealed that MRP4 silencing alters PANC1 gene expression, mainly dysregulating pathways related to cell-to-cell interactions and focal adhesion. Contrarily, MRP4 overexpression signifcantly increased BxPC-3 growth rate, produced a switch in the expression of EMT markers, and enhanced experimental metastatic incidence. Altogether, our results indicate that MRP4 is associated with a more aggressive phenotype in PDAC, boosting pancreatic tumorigenesis and metastatic capacity, which could fnally determine a fast tumor progression in PDAC patients.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/107878
url http://sedici.unlp.edu.ar/handle/10915/107878
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7450045&blobtype=pdf
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-020-71181-w
info:eu-repo/semantics/altIdentifier/issn/2045-2322
info:eu-repo/semantics/altIdentifier/pmid/32848164
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-71181-w
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
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reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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