ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology

Author:

Arconada-Luque ElenaORCID,Jiménez-Suarez Jaime,Pascual-Serra Raquel,Nam-Cha Syong Hyun,Moline Teresa,Cimas Francisco J.ORCID,Fliquete Germán,Ortega-Muelas Marta,Roche Olga,Fernández-Aroca Diego M.ORCID,Muñoz Velasco RaúlORCID,García-Flores Natalia,Garnés-García Cristina,Sánchez-Fdez AdriánORCID,Matilla-Almazán SofíaORCID,Sánchez-Arévalo Lobo Víctor J.ORCID,Hernández-Losa JavierORCID,Belandia Borja,Pandiella Atanasio,Esparís-Ogando AzucenaORCID,Ramón y Cajal SantiagoORCID,del Peso Luis,Sánchez-Prieto RicardoORCID,Ruiz-Hidalgo María JoséORCID

Abstract

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.

Funder

Ministerio de ciencia e innovación

Agencia Estatal de investigación

FEDER

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3