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Updated: Dec 9, 2025

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
11:28

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics

Published on: May 11, 2016

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Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO

Luis Francisco Lorenzo-Martín1,2,3, Mauricio Menacho-Márquez1,2,3, Xosé R Bustelo1,2,3

  • 1Centro de Investigación del Cáncer, CSIC-University of Salamanca, 37007 Salamanca, Spain.

Cancers
|September 9, 2020
PubMed

Insights

VAV2 drives a stem cell-like (SCL) program crucial for head and neck squamous cell carcinoma (hnSCC) development and progression. Targeting VAV2-regulated kinases offers potential therapeutic strategies for hnSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • VAV2, a guanine nucleotide exchange factor for RHO GTPases, is implicated in stem cell-like (SCL) regenerative proliferation.
  • This SCL program is vital for the tumorigenesis of cutaneous (cSCC) and head and neck squamous cell carcinomas (hnSCC).
  • Elevated VAV2 mRNA and VAV2-regulated gene signatures correlate with poor prognosis in human papillomavirus-negative hnSCC.

Purpose of the Study:

  • To investigate therapeutically actionable downstream targets within the VAV2-elicited SCL program in hnSCC.
  • To validate the role of VAV2-regulated kinases in the viability of undifferentiated and hnSCC-derived keratinocytes.

Main Methods:

  • Combined in silico and wet-lab approaches were employed.
  • Analysis of VAV2 mRNA levels and VAV2-regulated gene signatures.
  • Assessment of cell cycle- and signaling-related kinases essential for keratinocyte viability.

Main Results:

  • The VAV2-regulated SCL program includes cell cycle and signaling kinases critical for undifferentiated keratinocyte viability.
  • These kinases are also essential for the survival of hnSCC patient-derived cells with high VAV2 activity.
  • The VAV2-regulated SCL gene signature is linked to unfavorable prognosis in hnSCC patients.

Conclusions:

  • The VAV2-regulated SCL program plays a critical role in maintaining both preneoplastic and fully transformed keratinocytes.
  • This study identifies potential therapeutic targets within the VAV2 signaling pathway for hnSCC treatment.
  • VAV2's role in SCL program highlights its significance in hnSCC pathogenesis and therapeutic intervention.
Keywords:
GTPasesRac1RhoAVAV familyVAV2cancerhead and neckkeratinocytesoncogenesregenerative proliferationsignalingskinstem cells

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