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Updated: Mar 10, 2026

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

Jaime Jiménez-Suárez1, Francisco J Cimas1,2,3, José Joaquín Paricio1,4

  • 1Universidad de Castilla-La Mancha, Laboratorio de Oncología Molecular, Unidad de Medicina Molecular, Instituto de Biomedicina, Unidad Asociada de Biomedicina UCLM, Unidad Asociada al CSIC, Albacete, Spain.

International Journal of Biological Sciences
|March 9, 2026
PubMed

Insights

Extracellular matrix protein VCAN is a novel target of the ERK5 pathway in soft tissue sarcoma (STS). This ERK5/VCAN axis drives STS progression and presents a potential therapeutic target for this cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The ERK5 signaling pathway is increasingly recognized for its role in soft tissue sarcoma (STS) development and progression.
  • Understanding the molecular mechanisms underlying ERK5's function in STS is crucial for identifying new therapeutic strategies.

Purpose of the Study:

  • To identify novel downstream targets of ERK5 in STS.
  • To elucidate the role of VCAN (a chondroitin sulfate proteoglycan) as a mediator of ERK5-driven oncogenesis in STS.

Main Methods:

  • Utilized genetic manipulation (shRNA silencing, overexpression) and pharmacological inhibition of ERK5 in murine sarcoma models and human STS cell lines.
  • Performed transcriptomic profiling to assess VCAN's contribution to the ERK5 gene expression program.
  • Analyzed VCAN and ERK5 expression in human STS patient samples (leiomyosarcomas, undifferentiated pleomorphic sarcomas) and normal tissues.

Main Results:

  • Identified VCAN as a novel transcriptional target of ERK5, with ERK5 positively regulating VCAN expression.
  • Demonstrated that VCAN silencing phenocopies ERK5 silencing effects (impaired migration, adhesion, proliferation, tumorigenesis), while VCAN overexpression rescues these effects.
  • Found significantly elevated VCAN and ERK5 mRNA levels in human STS tissues compared to normal tissues, with a strong correlation between VCAN and ERK5 expression in specific STS subtypes.

Conclusions:

  • VCAN is a key effector in ERK5-mediated tumorigenesis and oncogenesis in soft tissue sarcomas.
  • The ERK5/VCAN signaling axis represents a promising therapeutic target for soft tissue sarcomas.
Keywords:
ERK5VCANadhesionmigrationsoft tissue sarcomatranscriptomics

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