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

Abstract

Annexin 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.

DCST1-AS1 Promotes TGF-β-Induced Epithelial–Mesenchymal Transition and Enhances Chemoresistance in Triple-Negative Breast Cancer Cells via ANXA1

“…Alli-Shaik et al analyzed mammary epithelial cells from ANXA1-hybrid and ANXA1-deficient mice by quantitative phosphorylation proteomics and found that most ANXA1-responsive phosphorylation changes occurred in proteins involved in cytoskeletal reorganization, which favors (30). Overexpression of ANXA1 is often associated with EMT in some aggressive cancers (31,32). TGF-β/Smad signaling plays an important role in the progression of EMT in breast cancer, in which phosphorylation of Smad2 triggers the formation of a complex between Smad2 and Smad4, resulting in nuclear translocation of the Smad2/Smad4 complex and subsequent gene transcription (12,33,34).…”

<p>The Metastasis Potential Promoting Capacity of Cancer-Associated Fibroblasts Was Attenuated by Cisplatin via Modulating KRT8</p>

“…AKT/NF-κB signaling pathway has been reported to play an important role in tumor cell proliferation, differentiation, and metastasis. 18 We examined the activation of AKT.…”

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

“…Breast tumor cell proliferation and migration were enhanced when ANXA1 was added, 9 and ANXA1-suppressed autophagy promoted nasopharyngeal carcinoma cell invasion and metastasis. 10 Another study reported that during oxygen-glucose deprivation, ANXA1 promoted microglial activation and migration. 11 We therefore determined whether exogeneous ANXA1-induced SC cellular proliferation and migration, thus, leading to nerve regeneration.…”