Abstract / Summary
Abstract Anoikis resistance (AR) is essential for the survival of circulating tumor cells for distant metastasis. However, the molecular mechanisms underlying AR survival and the promotion of further metastasis in head and neck squamous cell carcinoma (HNSCC) remain unclear. Here, we revealed that glycosylated PTX3 was enriched in AR cells in response to oxidative stress. The depletion of PTX3 significantly inhibited spheroid formation and survival, invasiveness, extravasation, and the formation of metastatic lung nodules in AR cells of HNSCC. Mechanically, moderate ROS levels in AR cells induced protective autophagy through the activation of EGFR, followed by upregulation of PTX3 expression regulated by the expression of ATG5/12, resulting in increased survivin expression. In contrast, inhibition of autophagy attenuated PTX3 expression and reduced anoikis resistance and metastasis. These results reveal that targeting protective autophagy-regulated factors, such as PTX3, can effectively inhibit HNSCC AR cell survival and metastasis.