Repositorio Institucional
Repositorio Institucional
CONICET Digital
  • Inicio
  • EXPLORAR
    • AUTORES
    • DISCIPLINAS
    • COMUNIDADES
  • Estadísticas
  • Novedades
    • Noticias
    • Boletines
  • Ayuda
    • General
    • Datos de investigación
  • Acerca de
    • CONICET Digital
    • Equipo
    • Red Federal
  • Contacto
JavaScript is disabled for your browser. Some features of this site may not work without it.
  • INFORMACIÓN GENERAL
  • RESUMEN
  • ESTADISTICAS
 
Artículo

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

Sahores, AnaIcon ; Carozzo, A.; May, M.; Gomez, NataliaIcon ; Di Siervi, NicolásIcon ; de Sousa Serro, Maximiliano GuillermoIcon ; Yaneff, AgustínIcon ; Rodriguez Gonzalez, Angela PaolaIcon ; Abba, Martín CarlosIcon ; Shayo, Carina ClaudiaIcon ; Davio, Carlos AlbertoIcon
Fecha de publicación: 08/2020
Editorial: Nature
Revista: Scientific Reports
ISSN: 2045-2322
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Farmacología y Farmacia

Resumen

Recent findings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the significance 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 significantly 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 finally determine a fast tumor progression in PDAC patients.
Palabras clave: MRP4 , PDAC , BIOMARKER , TERAPEUTHYCAL TARGET
Ver el registro completo
 
Archivos asociados
Thumbnail
 
Tamaño: 8.140Mb
Formato: PDF
.
Descargar
Licencia
info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/139092
URL: http://www.nature.com/articles/s41598-020-71181-w
DOI: http://dx.doi.org/10.1038/s41598-020-71181-w
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Citación
Sahores, Ana; Carozzo, A.; May, M.; Gomez, Natalia; Di Siervi, Nicolás; et al.; Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness; Nature; Scientific Reports; 10; 1; 8-2020; 1-15
Compartir
Altmétricas
 

Enviar por e-mail
Separar cada destinatario (hasta 5) con punto y coma.
  • Facebook
  • X Conicet Digital
  • Instagram
  • YouTube
  • Sound Cloud
  • LinkedIn

Los contenidos del CONICET están licenciados bajo Creative Commons Reconocimiento 2.5 Argentina License

https://www.conicet.gov.ar/ - CONICET

Inicio

Explorar

  • Autores
  • Disciplinas
  • Comunidades

Estadísticas

Novedades

  • Noticias
  • Boletines

Ayuda

Acerca de

  • CONICET Digital
  • Equipo
  • Red Federal

Contacto

Godoy Cruz 2290 (C1425FQB) CABA – República Argentina – Tel: +5411 4899-5400 repositorio@conicet.gov.ar
TÉRMINOS Y CONDICIONES