NRP-1, a co-receptor of the EGFR, represented an interesting candidate to investigate in HNSCC, as Cetuximab, in combination with radio and chemotherapy, provided the first
targeted therapy scheme approved by the FDA as a standard of care for patients with recurrent or
metastatic HNSCC. High levels of NRP-1 expression significantly correlated with a shorter overall
survival in both Oral Squamous Cell Carcinoma and Oropharyngeal Squamous Cell Carcinoma diagnosed patients, suggesting a prognostic role for this protein. In HNSCC cell lines in vitro experiments,
NRP-1 sustained EGFR activation upon CDDP exposure, together with activation of downstream
MAPK/AKT pathways. Furthermore, NRP-1 modulated the responsiveness to CDDP treatment.
Head and neck squamous cell carcinoma (HNSCC) includes a group of aggressive malignancies 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.