Background: Though metastasis is the leading cause of death in patients with head and neck squamous cell carcinoma (HNSCC), fundamental questions about the mechanisms that enable or inhibit metastasis remain unanswered. CD63, a tetraspanin family member, has been linked to tumor progression and metastasis. However, few studies have examined the role of CD63 in HNSCC.
Methods: We discovered CD63 expression in paired HNSCC tissue by tissue microarray. Cell phenotype experiments and lung metastasis mouse model were adopted to investigate the effect of CD63 on tumour metastasis in vitro and vivo. The molecular mechanism was investigated by mass spectrometry, Co-IP, immunofluorescence analysis and molecular docking.
Results: CD63 expression was abnormally decreased in HNSCC tissue compared to adjacent tissue, and that this was linked to prognosis. Overexpression of CD63 inhibited the progression and metastasis of HNSCC cells. KRT1 could be a direct interacting partner of CD63. CD63 reduces HNSCC progression via KRT1-mediated cell cycle arrest. Both CD63 and KRT1 expression was significantly decreased in metastatic tissue compared with primary tumor tissue.
Conclusions: We reveal a previously unrecognized role of CD63 in HNSCC cells. Our findings contribute to defining an important mechanism of HNSCC progression and metastasis.