Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activation

Abstract

AbstractAnnexin A1 (ANXA1) is dysregulated in the various tumors. However, the role and mechanism of ANXA1 in the cancers are poorly understood. In this study, we first showed a clinically positive correlation between ANXA1 and autophagy-associated protein SQSTM1 expression in nasopharyngeal carcinoma (NPC) and ANXA1-regulating SQSTM1 expression through autophagy, and further demonstrated that ANXA1 inhibited BECN1 and ATG5-dependent autophagy in the NPC cells. Using phospho-kinase antibody array to identify signaling through which ANXA1 regulated NPC cell autophagy, we found that ANXA1-suppressed autophagy was associated with PI3K/AKT signaling activation. We also showed that ANXA1 expression was significantly increased in the NPCs with metastasis relative to NPCs without metastasis and positively correlated with lymphonode and distant metastasis; high ANXA1 expression in the NPC cells promoted in vitro tumor cell migration and invasion and in vivo metastasis. Lastly, we showed that inhibition of autophagy restored the ability of tumor cell migration and invasion, epithelial–mesenchymal transition (EMT)-like alterations and in vivo metastasis in the ANXA1 knockdown NPC cells with autophagy activation; ANXA1-suppresed autophagy induced EMT-like alterations possibly by inhibiting autophagy-mediated degradation of Snail. Our data suggest that ANXA1-suppressed autophagy promotes NPC cell migration, invasion and metastasis by activating PI3K/AKT signaling pathway, highlighting that the activation of autophagy may inhibit metastasis of NPC with high ANXA1 expression.