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

Autores
Davio, Carlos Alberto
Año de publicación
2021
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Pancreatic ductal adenocarcinoma (PDAC) is one of themost lethal human malignancies, due to its late diagnosis,inherent resistance to treatment and early dissemination.This type of tumor is expected to become the secondleading cause of cancer mortality by the year 2030and has limited therapeutic options. Even after the developmentof new targeted agents and the use of multipletherapeutic combinations, there is no clear benefit for thisdisease. Recent findings from our laboratory show thatMRP4 is critical for PDAC cell proliferation. Nevertheless,the significance of MRP4 protein levels and functionin PDAC progression is still unclear. Bioinformaticstudies revealed that PDAC samples show higher MRP4transcript levels compared to normal adjacent pancreatictissue and circulating tumor cells express higher levelsof MRP4 than primary tumors. Also, high levels of MRP4are typical of high-grade PDAC cell lines and associatewith an epithelial-mesenchymal phenotype. Moreover,PDAC patients with high levels of MRP4 depict dysregulationof pathways associated with migration, chemotaxisand cell adhesion. Silencing MRP4 in PANC1 cells reducedtumorigenicity and tumor growth and impaired cellmigration. Transcriptomic analysis revealed that MRP4silencing alters PANC1 gene expression, mainly dysregulatingpathways related to cell-to-cell interactions andfocal adhesion. Contrarily, overexpression of MRP4 inBxPC-3 cells produced a switch in the expression of EMTmarkers, significantly increased tumor growth, and enhancedexperimental metastatic incidence. Overall, ourfindings indicate that MRP4 upregulation could representan adaptive advantage associated with poor prognosis,evidenced by the co-expression of mesenchymal markers,higher cell proliferation, tumorigenicity and invasivenessin PDAC models. Thus, we provide theoretical andexperimental support for targeted treatment of pancreaticcancer by making an important contribution to the understandingof pancreatic tumor cell biology.
Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
XV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina De Investigación Clínica
Sociedad Argentina De Inmunología
Sociedad Argentina De Fisiología
Materia
MRP4
PANCREATIC CANCER
cAMP
BIOMARKER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/246967
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressivenessDavio, Carlos AlbertoMRP4PANCREATIC CANCERcAMPBIOMARKERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Pancreatic ductal adenocarcinoma (PDAC) is one of themost lethal human malignancies, due to its late diagnosis,inherent resistance to treatment and early dissemination.This type of tumor is expected to become the secondleading cause of cancer mortality by the year 2030and has limited therapeutic options. Even after the developmentof new targeted agents and the use of multipletherapeutic combinations, there is no clear benefit for thisdisease. Recent findings from our laboratory show thatMRP4 is critical for PDAC cell proliferation. Nevertheless,the significance of MRP4 protein levels and functionin PDAC progression is still unclear. Bioinformaticstudies revealed that PDAC samples show higher MRP4transcript levels compared to normal adjacent pancreatictissue and circulating tumor cells express higher levelsof MRP4 than primary tumors. Also, high levels of MRP4are typical of high-grade PDAC cell lines and associatewith an epithelial-mesenchymal phenotype. Moreover,PDAC patients with high levels of MRP4 depict dysregulationof pathways associated with migration, chemotaxisand cell adhesion. Silencing MRP4 in PANC1 cells reducedtumorigenicity and tumor growth and impaired cellmigration. Transcriptomic analysis revealed that MRP4silencing alters PANC1 gene expression, mainly dysregulatingpathways related to cell-to-cell interactions andfocal adhesion. Contrarily, overexpression of MRP4 inBxPC-3 cells produced a switch in the expression of EMTmarkers, significantly increased tumor growth, and enhancedexperimental metastatic incidence. Overall, ourfindings indicate that MRP4 upregulation could representan adaptive advantage associated with poor prognosis,evidenced by the co-expression of mesenchymal markers,higher cell proliferation, tumorigenicity and invasivenessin PDAC models. Thus, we provide theoretical andexperimental support for targeted treatment of pancreaticcancer by making an important contribution to the understandingof pancreatic tumor cell biology.Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina De Investigación ClínicaSociedad Argentina De InmunologíaSociedad Argentina De FisiologíaFundación Revista Medicina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/246967Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness; XV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2020; 1-10025-7680CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:51Zoai:ri.conicet.gov.ar:11336/246967instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:51.282CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
Davio, Carlos Alberto
MRP4
PANCREATIC CANCER
cAMP
BIOMARKER
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 Davio, Carlos Alberto
author Davio, Carlos Alberto
author_facet Davio, Carlos Alberto
author_role author
dc.subject.none.fl_str_mv MRP4
PANCREATIC CANCER
cAMP
BIOMARKER
topic MRP4
PANCREATIC CANCER
cAMP
BIOMARKER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Pancreatic ductal adenocarcinoma (PDAC) is one of themost lethal human malignancies, due to its late diagnosis,inherent resistance to treatment and early dissemination.This type of tumor is expected to become the secondleading cause of cancer mortality by the year 2030and has limited therapeutic options. Even after the developmentof new targeted agents and the use of multipletherapeutic combinations, there is no clear benefit for thisdisease. Recent findings from our laboratory show thatMRP4 is critical for PDAC cell proliferation. Nevertheless,the significance of MRP4 protein levels and functionin PDAC progression is still unclear. Bioinformaticstudies revealed that PDAC samples show higher MRP4transcript levels compared to normal adjacent pancreatictissue and circulating tumor cells express higher levelsof MRP4 than primary tumors. Also, high levels of MRP4are typical of high-grade PDAC cell lines and associatewith an epithelial-mesenchymal phenotype. Moreover,PDAC patients with high levels of MRP4 depict dysregulationof pathways associated with migration, chemotaxisand cell adhesion. Silencing MRP4 in PANC1 cells reducedtumorigenicity and tumor growth and impaired cellmigration. Transcriptomic analysis revealed that MRP4silencing alters PANC1 gene expression, mainly dysregulatingpathways related to cell-to-cell interactions andfocal adhesion. Contrarily, overexpression of MRP4 inBxPC-3 cells produced a switch in the expression of EMTmarkers, significantly increased tumor growth, and enhancedexperimental metastatic incidence. Overall, ourfindings indicate that MRP4 upregulation could representan adaptive advantage associated with poor prognosis,evidenced by the co-expression of mesenchymal markers,higher cell proliferation, tumorigenicity and invasivenessin PDAC models. Thus, we provide theoretical andexperimental support for targeted treatment of pancreaticcancer by making an important contribution to the understandingof pancreatic tumor cell biology.
Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
XV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina De Investigación Clínica
Sociedad Argentina De Inmunología
Sociedad Argentina De Fisiología
description Pancreatic ductal adenocarcinoma (PDAC) is one of themost lethal human malignancies, due to its late diagnosis,inherent resistance to treatment and early dissemination.This type of tumor is expected to become the secondleading cause of cancer mortality by the year 2030and has limited therapeutic options. Even after the developmentof new targeted agents and the use of multipletherapeutic combinations, there is no clear benefit for thisdisease. Recent findings from our laboratory show thatMRP4 is critical for PDAC cell proliferation. Nevertheless,the significance of MRP4 protein levels and functionin PDAC progression is still unclear. Bioinformaticstudies revealed that PDAC samples show higher MRP4transcript levels compared to normal adjacent pancreatictissue and circulating tumor cells express higher levelsof MRP4 than primary tumors. Also, high levels of MRP4are typical of high-grade PDAC cell lines and associatewith an epithelial-mesenchymal phenotype. Moreover,PDAC patients with high levels of MRP4 depict dysregulationof pathways associated with migration, chemotaxisand cell adhesion. Silencing MRP4 in PANC1 cells reducedtumorigenicity and tumor growth and impaired cellmigration. Transcriptomic analysis revealed that MRP4silencing alters PANC1 gene expression, mainly dysregulatingpathways related to cell-to-cell interactions andfocal adhesion. Contrarily, overexpression of MRP4 inBxPC-3 cells produced a switch in the expression of EMTmarkers, significantly increased tumor growth, and enhancedexperimental metastatic incidence. Overall, ourfindings indicate that MRP4 upregulation could representan adaptive advantage associated with poor prognosis,evidenced by the co-expression of mesenchymal markers,higher cell proliferation, tumorigenicity and invasivenessin PDAC models. Thus, we provide theoretical andexperimental support for targeted treatment of pancreaticcancer by making an important contribution to the understandingof pancreatic tumor cell biology.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/246967
Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness; XV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2020; 1-1
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/246967
identifier_str_mv Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness; XV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2020; 1-1
0025-7680
CONICET Digital
CONICET
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicina
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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