Neuropilin-1 expression associates with poor prognosis in HNSCC and elicits EGFR activation upon CDDP-induced cytotoxic stress

Virginia Napolitano, Daniela Russo, Francesco Morra, Francesco Merolla, Silvia Varricchio, Gennaro Ilardi, Rosa Maria Di Crescenzo, Francesco Martino, Massimo Mascolo, Angela Celetti, Luca Tamagnone, Stefania Staibano

Research output: Contribution to journalArticlepeer-review

Abstract

Head and neck squamous cell carcinoma (HNSCC) includes a group of aggressive malig-nancies characterized by the overexpression of the epidermal growth factor receptor (EGFR) in 90% of cases. Neuropilin-1 (NRP-1) acts as an EGFR co-receptor, enhancing, upon ligand stimulation, EGFR signaling in several cellular models. However, NRP-1 remains poorly characterized in HNSCC. By utilizing in vitro cellular models of HNSCC, we report that NRP-1 is involved in the regulation of EGFR signaling. In fact, NRP-1 can lead to cisplatin-induced EGFR phosphorylation, an escape mechanism activated by cancer cells upon cytotoxic stress. Furthermore, we evaluated Neuropilin-1 staining in tissue samples of an HNSCC case series (n = 218), unraveling a prognostic value for the Neuropilin-1 tissue expression. These data suggest a potential role for NRP-1 in HNSCC cancer progression, expanding the repertoire of signaling in which NRP-1 is involved and eliciting the need for further investigations on NRP-1 as a suitable target for HNSCC novel therapeutic approaches.

Original languageEnglish
Article number3822
JournalCancers
Volume13
Issue number15
DOIs
Publication statusPublished - Aug 1 2021

Keywords

  • Cisplatin
  • EGFR
  • HNSCC
  • NRP-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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