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Título: | ERK5 Is a major determinant of chemical sarcomagenesis: implications in human pathology |
Autor: | Arconada-Luque, Elena; Jiménez-Suárez, Jaime; Pascual-Serra, Raquel; Hyun Nam-Cha, Syong; Moline, Teresa; Cimas, Francisco J.; Fliquete, Germán; Ortega-Muelas, Marta; Roche, Olga CSIC ORCID; Fernández-Aroca, Diego M.; Muñoz Velasco, Raúl; García-Flores, Natalia; Garnés-García, Cristina; Sánchez-Fdez, Adrián ; Matilla-Almazán, Sofía; Sánchez-Arévalo Lobo, Víctor J.; Hernández-Losa, Javier; Belandia, Borja CSIC ORCID; Pandiella, Atanasio CSIC ORCID CVN ; Esparís-Ogando, Azucena CSIC ORCID ; Ramón y Cajal, Santiago; Peso, Luis del CSIC ORCID; Sánchez-Prieto, Ricardo CSIC ORCID; Ruiz-Hidalgo, María J. | Palabras clave: | ERK5 MAPK7 Soft tissue sarcoma Leiomyosarcoma rhabdomyosarcoma KLF2 3-methyl-cholanthrene |
Fecha de publicación: | 2022 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | Cancers 14(14): 3509 (2022) | Resumen: | Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology. | Versión del editor: | http://dx.doi.org/10.3390/cancers14143509 | URI: | http://hdl.handle.net/10261/283795 | DOI: | 10.3390/cancers14143509 | Identificadores: | doi: 10.3390/cancers14143509 e-issn: 2072-6694 |
Aparece en las colecciones: | (IBMCC) Artículos (IIBM) Artículos |
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ERK5 Is a Major Determinant_Arconada_PV_Art2022.pdf | 9,45 MB | Adobe PDF | Visualizar/Abrir |
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