VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma

The ERK5 signaling pathway has recently emerged as a critical regulator of soft tissue sarcoma (STS) biology, contributing to tumor initiation, progression, and maintenance. In this study, we identify VCAN, a chondroitin sulfate proteoglycan, as a novel transcriptional target of ERK5 and a central m...

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Detalles Bibliográficos
Autores: Jiménez Suárez, Jaime, Cimas Felipe, Francisco José, Paricio, José Joaquín, Belandia, Borja, Berrouayel, Yosra, Arconada Luque, Elena, Matilla Almazán, Sofía, Soffientini, Cesare, Percio, Stefano, Redondo García, Silvia, García Flores, Natalia, Gárnes García, Cristina, Fernández Aroca, Pablo, Martínez Gómez, Juan Jesús, Fernández Aramburo, Antonio, Nam Cha, Syong Hyum, Rovida, Elisabetta, Pandiella, Atanasio, Esparís Ogando, Azucena, Pasquali, Sandro, Rodríguez Manzaneque, Juan Carlos, Peso, Luis del, Ruiz Hidalgo, María José, Sánchez Prieto, Ricardo
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/47966
Acceso en línea:https://hdl.handle.net/10578/47966
Access Level:acceso abierto
Palabra clave:Adhesion
ERK5
Migration
Soft tissue sarcoma
Transcriptomics
VCAN
Descripción
Sumario:The ERK5 signaling pathway has recently emerged as a critical regulator of soft tissue sarcoma (STS) biology, contributing to tumor initiation, progression, and maintenance. In this study, we identify VCAN, a chondroitin sulfate proteoglycan, as a novel transcriptional target of ERK5 and a central mediator of ERK5-related oncogenesis. Through a combination of genetic (silencing, overexpression) and pharmacological approaches, applied in both a chemically induced murine sarcoma model and several human STS cell lines, we demonstrate that ERK5 positively regulates VCAN expression. Functionally, VCAN silencing (by shRNAs) recapitulates the phenotypes of ERK5 silencing, including impaired migration, adhesion, proliferation, and tumorigenesis. Conversely, VCAN overexpression rescues these effects, confirming its essential role in ERK5-mediated oncogenesis. Furthermore, transcriptomic profiling reveals that VCAN accounts for a substantial portion of ERK5-regulated gene expression program. Analyses of human STS patient samples reveal significantly elevated mRNA levels of both VCAN and ERK5 compared to normal tissues. Notably, a strong correlation between VCAN and ERK5 expression, both at mRNA and protein levels, emerged in biopsies from leiomyosarcomas and undifferentiated pleomorphic sarcomas. Together, these findings uncover VCAN as a key effector in ERK5-driven tumorigenesis and highlight the ERK5/VCAN signaling axis as a promising therapeutic target in soft tissue sarcomas.

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