RT Journal Article
T1 PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation.
A1 Rodríguez, María Isabel
A1 Peralta-Leal, Andreína
A1 O'Valle, Francisco
A1 Rodriguez-Vargas, José Manuel
A1 Gonzalez-Flores, Ariannys
A1 Majuelos-Melguizo, Jara
A1 López, Laura
A1 Serrano, Santiago
A1 García de Herreros, Antonio
A1 Rodríguez-Manzaneque, Juan Carlos
A1 Fernández, Rubén
A1 Moral, Raimundo G Del
A1 Almodóvar, José Mariano de
A1 Oliver, F Javier
K1 Antígenos CD
K1 Neoplasias de la Mama
K1 Cadherinas
K1 Línea Celular Tumoral
K1 Transformación Celular Neoplásica
K1 Perros
K1 Células Endoteliales
K1 Transición Epitelial-Mesenquimal
K1 Femenino
K1 Regulación Neoplásica de la Expresión Génica
K1 Células Endoteliales de la Vena Umbilical Humana
K1 Humanos
K1 Células MCF-7
K1 Ratones
K1 Melanoma Experimental
K1 Invasividad Neoplásica
K1 Metástasis de la Neoplasia
K1 Poli(ADP-Ribosa) Polimerasas
K1 Vimentina
AB PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.
SN 1553-7390
YR 2013
FD 2013-06-13
LK http://hdl.handle.net/10668/1640
UL http://hdl.handle.net/10668/1640
LA en
NO Rodríguez MI, Peralta-Leal A, O'Valle F, Rodriguez-Vargas JM, Gonzalez-Flores A, Majuelos-Melguizo J, et al. PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. PLoS Genet.. 2013 ; 9(6):e1003531
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 12, 2025