Artículo
Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
Sahores, Ana
; Carozzo, A.; May, M.; Gomez, Natalia
; Di Siervi, Nicolás
; de Sousa Serro, Maximiliano Guillermo
; Yaneff, Agustín
; Rodriguez Gonzalez, Angela Paola
; Abba, Martín Carlos
; Shayo, Carina Claudia
; Davio, Carlos Alberto
Fecha de publicación:
08/2020
Editorial:
Nature
Revista:
Scientific Reports
ISSN:
2045-2322
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
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
Archivos asociados
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Identificadores
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
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
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