Antagonizing Sec62 function in intracellular Ca homeostasis represents a novel therapeutic strategy for head and neck cancer.

Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine model. Additionally, a CRISPR/Cas9 based knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy .