1. ERK5 is a major determinant of chemical sarcomagenesis: implications in human pathology
- Author
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Elena Arconada-Luque, Jaime Jiménez-Suarez, Raquel Pascual-Serra, Syong Hyun Nam-Cha, Teresa Moline, Francisco J. Cimas, Germán Fliquete, Marta Ortega-Muelas, Olga Roche, Diego M. Fernández-Aroca, Raúl Muñoz Velasco, Natalia García-Flores, Cristina Garnés-García, Adrián Sánchez-Fdez, Sofía Matilla-Almazán, Víctor J. Sánchez-Arévalo Lobo, Javier Hernández-Losa, Borja Belandia, Atanasio Pandiella, Azucena Esparís-Ogando, Santiago Ramón y Cajal, Luis del Peso, Ricardo Sánchez-Prieto, María José Ruiz-Hidalgo, UAM. Departamento de Bioquímica, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Fundación Leticia Castillejo, Roche, Acepain Albacete, Universidad de Castilla La Mancha, Junta de Comunidades de Castilla-La Mancha, Institut Català de la Salut, [Arconada-Luque E, Jiménez-Suarez J, Pascual-Serra R] Laboratorio de Oncología Molecular, Unidad de Medicina Molecular, Centro Regional de Investigaciones Biomédicas, Unidad Asociada de Biomedicina UCLM, Unidad Asociada al CSIC, Universidad de Castilla-La Mancha, Albacete, Spain. [Nam-Cha SH] Servicio de Anatomía Patológica, Hospital General de Albacete, Albacete, Spain. [Moline T, Fliquete G, Hernández-Losa J, Ramón Y Cajal S] Grup de Recerca en Patologia Molecular Traslacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en RED de Cáncer CIBERONC, Barcelona, Spain. [Cimas FJ] Unidad de Bioquímica y Biología Molecular, Servicio de Instrumentación Biomédica, Universidad de Castilla-La Mancha, Albacete, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Leiomyosarcoma ,Cancer Research ,Medicina ,Otros calificadores::/diagnóstico [Otros calificadores] ,Neoplasms::Neoplasms by Site::Soft Tissue Neoplasms [DISEASES] ,neoplasias [ENFERMEDADES] ,Rhabdomyosarcoma ,MAPK7 ,Other subheadings::/diagnosis [Other subheadings] ,Sarcoma - Tractament ,neoplasias::neoplasias por localización::neoplasias de los tejidos blandos [ENFERMEDADES] ,Otros calificadores::/terapia [Otros calificadores] ,3-methyl-cholanthrene ,Soft tissue sarcoma ,KLF2 ,Other subheadings::/therapy [Other subheadings] ,leiomyosarcoma ,Neoplasms [DISEASES] ,ERK5 ,Oncology ,soft tissue sarcoma ,rhabdomyosarcoma ,Sarcoma - Diagnòstic ,Cèl·lules canceroses - Abstract
Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAM, 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, This work has been supported with Grant RTI2018-094093-B-I00 funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” to RSP. Also supported with funds from Fundación Leticia Castillejo Castillo, Roche España and ACEPAIN to RSP and MJRH. RSP and MJRH’s Research Institute and the work carried out in their laboratory, received partial support from the European Community through the FEDER. JJ and EAL hold a predoctoral research contract cofounded by the European Social Fund and UCLM. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013)
- Published
- 2022