Desmoglein 1 regulates invadopodia by suppressing EGFR/ERK signaling in an ERBIN-dependent manner

Alejandra Valenzuela-Iglesias, Hope E. Burks, Christopher R. Arnette, Amulya Yalamanchili, Oxana Nekrasova, Lisa M. Godsel, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Loss of the desmosomal cell–cell adhesion molecule, Desmoglein 1 (Dsg1), has been reported as an indicator of poor prognosis in head and neck squamous cell carcinomas (HNSCC) overexpressing epidermal growth factor receptor (EGFR). It has been well established that EGFR signaling promotes the formation of invadopodia, actin-based protrusions formed by cancer cells to facilitate invasion and metastasis, by activating pathways leading to actin polymerization and ultimately matrix degradation. We previously showed that Dsg1 downregulates EGFR/Erk signaling by interacting with the ErbB2-binding protein Erbin (ErbB2 Interacting Protein) to promote keratinocyte differentiation. Here, we provide evidence that restoring Dsg1 expression in cells derived from HNSCC suppresses invasion by decreasing the number of invadopodia and matrix degradation. Moreover, Dsg1 requires Erbin to downregulate EGFR/Erk signaling and to fully suppress invadopodia formation. Our findings indicate a novel role for Dsg1 in the regulation of invadopodia signaling and provide potential new targets for development of therapies to prevent invadopodia formation and therefore cancer invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)1195-1206
Number of pages12
JournalMolecular Cancer Research
Volume17
Issue number5
DOIs
StatePublished - May 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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