Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness
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. Bioi...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2020
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/107878 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7450045&blobtype=pdf https://www.nature.com/articles/s41598-020-71181-w |
| Aporte de: |
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I19-R120-10915-107878 |
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| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Medicina cancer pancreatic cancer |
| spellingShingle |
Medicina cancer pancreatic cancer 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. Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness |
| topic_facet |
Medicina cancer pancreatic cancer |
| 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. |
| format |
Articulo Articulo |
| author |
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_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_sort |
Sahores, A. |
| title |
Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness |
| 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 |
| publishDate |
2020 |
| url |
http://sedici.unlp.edu.ar/handle/10915/107878 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7450045&blobtype=pdf https://www.nature.com/articles/s41598-020-71181-w |
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