AHNAK Downregulation Contributes to Nasopharyngeal Carcinoma Tumorigenesis and Metastasis

Abstract Purpose Nasopharyngeal carcinoma (NPC) is an aggressive head and neck disease with a high incidence of distant metastases. Enlargeosomes are cytoplasmic organelles marked by, desmoyokin/AHNAK. The purpose of this study was to evaluate the expression of AHNAK in NPC and its effect on enlargeosomes, and to investigate the correlation between AHNAK expression levels and clinical NPC patient characteristics. Methods Primary nasopharyngeal carcinoma (NPC) and NPC specimens were evaluated by analyzing public data, immunohistochemistry. Systematic in vitro and in vivo experiments were performed using different NPC-derived cell lines and mouse models. Results In this study, we detected AHNAK and Annexin A2(ANXA2), a protein coating the surface of enlargeosomes, in NPC samples. We found that AHNAK was down-regulated, whereas Annexin A2 was upregulated in human NPC tissues. Down-regulation of AHNAK was associated with poor overall survival in NPC patients. Upregulation of Annexin A2 was associated with lymph node metastasis and distant metastasis in NPC patients. Functional studies confirmed that silencing of AHNAK enhanced the growth, invasion, and metastatic properties of NPC cells both in vitro and in vivo. In terms of mechanism, loss of AHNAK led to increase of annexin A2 protein level in NPC cells. Silencing ANXA2 restored the migrative and invasive ability of NPC cells upon loss of AHNAK. Moreover, transcription factor FOSL1-mediated transcriptional repression was responsible for the low-expression of AHNAK by recruiting EZH2. Conclusion Here, we report AHNAK as a tumor suppressor in NPC, which may act through annexin A2 oncogenic signaling in enlargeosome, with potential implications for novel approaches to NPC treatment.