Interestingly, we also observed upregulations of genes involved in axonal guidance-L1 cell adhesion molecule ( L1CAM), neuropilin-1, semaphorins, and ephrins, indicating potential interactions of cancer cells and neuronal components of the stroma. This profile overlapped partially with the expression of signature genes related to the partial EMT available from the single cell analysis of human HNSCC specimens, highlighting the relevance of our data to the clinical disease progression state. A functional genomic study unveiled genes involved in cellular movement and invasion providing a molecular profile of HNSCC invasive cells. The analyses of tumors revealed that Catulin-green fluorescent protein (GFP)-positive cells were enriched in clusters of cells at the tumor invasion front. Here, we developed a novel catulin promoter-based reporter system that allows us to isolate and characterize in vivo a small fraction of invasive cancer cells. Partial or more complete epithelial–mesenchymal transition (EMT) plays a role in tumor progression however, it remains a challenge to observe the EMT in vivo, due to its transient nature. Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with a poor prognosis due to late diagnosis and loco-regional metastasis.

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