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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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
Formato: artículo
Fecha de publicación:2026
País:España
Recursos:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/47966
Acesso em linha:https://hdl.handle.net/10578/47966
Access Level:acceso abierto
Palavra-chave:Adhesion
ERK5
Migration
Soft tissue sarcoma
Transcriptomics
VCAN
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spelling VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue SarcomaJiménez Suárez, JaimeCimas Felipe, Francisco JoséParicio, José JoaquínBelandia, BorjaBerrouayel, YosraArconada Luque, ElenaMatilla Almazán, SofíaSoffientini, CesarePercio, StefanoRedondo García, SilviaGarcía Flores, NataliaGárnes García, CristinaFernández Aroca, PabloMartínez Gómez, Juan JesúsFernández Aramburo, AntonioNam Cha, Syong HyumRovida, ElisabettaPandiella, AtanasioEsparís Ogando, AzucenaPasquali, SandroRodríguez Manzaneque, Juan CarlosPeso, Luis delRuiz Hidalgo, María JoséSánchez Prieto, RicardoAdhesionERK5MigrationSoft tissue sarcomaTranscriptomicsVCANThe 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.Ivyspring International Publisher202620262026info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/47966reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésPID2021-122222OB-I00PID2019-104416RB-I002025-GRIN-38249SBPLY/23/180225/000007BRI2017PID2020-118821RB-I00SBPLY/23/180225/000007UCLM 2020-PREDUCLM-15144PID2020-115605RB-I00PI19/00840IG 2018-ID. 21349 projectinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/479662026-05-27T07:36:41Z
dc.title.none.fl_str_mv VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
title VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
spellingShingle VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
Jiménez Suárez, Jaime
Adhesion
ERK5
Migration
Soft tissue sarcoma
Transcriptomics
VCAN
title_short VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
title_full VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
title_fullStr VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
title_full_unstemmed VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
title_sort VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma
dc.creator.none.fl_str_mv 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
author Jiménez Suárez, Jaime
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adhesion
ERK5
Migration
Soft tissue sarcoma
Transcriptomics
VCAN
topic Adhesion
ERK5
Migration
Soft tissue sarcoma
Transcriptomics
VCAN
description 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.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/47966
url https://hdl.handle.net/10578/47966
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PID2021-122222OB-I00
PID2019-104416RB-I00
2025-GRIN-38249
SBPLY/23/180225/000007
BRI2017
PID2020-118821RB-I00
SBPLY/23/180225/000007
UCLM 2020-PREDUCLM-15144
PID2020-115605RB-I00
PI19/00840
IG 2018-ID. 21349 project
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Ivyspring International Publisher
publisher.none.fl_str_mv Ivyspring International Publisher
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414680572723200
score 15,811543

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