Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.

Background: Head and neck squamous cell carcinoma (HNSCC) is more prevalent in men than women and this disparity cannot be fully explained by known risk factors. Recent studies have shown that loss of Y chromosome (LoY) confers an increased risk of solid cancer and reduces life expectancy in men.Methods: Using publicly available data from The Cancer Genome Atlas, we investigated the prevalence of LoY and its association with clinicopathological features in male HNSCC.Results: LoY was detectable in around 25% of male HNSCC. Men with human papillomavirus‐negative tumors exhibiting LoY experienced significantly worse overall survival than those with no LoY. Moreover, LoY tumors exhibited overexpression of genes involved in redox processes, including genes previously implicated in resistance to both radiotherapy and cisplatin‐based chemotherapeutics.Conclusion: LoY may be an indicator of poor prognosis in male HNSCC that is linked to the overexpression of genes associated with resistance to standard care therapies.