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YB-1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

Karin Schelch1,2, Sebastian Eder1, Benjamin Zitta1

  • 1Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria.

Molecular Oncology
|December 23, 2022
PubMed

Insights

Y-box-binding protein-1 (YB-1) drives aggressive pleural mesothelioma (PM) cell behavior and migration. Inhibiting YB-1 reduces PM cell motility, offering potential therapeutic strategies for this challenging cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pleural mesothelioma (PM) exhibits aggressive traits like rapid growth and local invasion, with limited treatment options.
  • The oncoprotein Y-box-binding protein-1 (YB-1) is frequently overexpressed in various cancers, correlating with aggressive behavior.

Purpose of the Study:

  • To investigate the role of YB-1 in regulating target genes and influencing the behavior of pleural mesothelioma cells.
  • To elucidate the mechanisms by which YB-1 contributes to the aggressive phenotype of PM.

Main Methods:

  • Utilized siRNA-mediated knockdown and inducible overexpression of YB-1 in PM cells.
  • Assessed cell motility, migration, and intravasation in vitro and in zebrafish models.
  • Analyzed mRNA and protein levels of key regulatory genes, including EGFR, snail, MMP1, EPHA5, and PARK2.

Main Results:

  • YB-1 overexpression increased PM cell scattering, migration, and intravasation, while knockdown reduced cell motility.
  • YB-1 influenced the expression of EGFR and snail, and partially regulated MMP1, EPHA5, and PARK2.
  • Snail was identified as a critical mediator of YB-1-induced cell motility in PM.

Conclusions:

  • YB-1 plays a significant role in the aggressive nature of pleural mesothelioma by regulating cell migration.
  • YB-1's effects on PM cell motility are mediated, in part, through the regulation of EGFR and snail.
  • Targeting YB-1 presents a potential therapeutic strategy for managing PM progression.
Keywords:
EGFRYB‐1cell migrationpleural mesotheliomasnail

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