Foxq1 promotes metastasis of nasopharyngeal carcinoma by inducing vasculogenic mimicry via the EGFR signaling pathway.

Abstract

In nasopharyngeal carcinoma (NPC), the treatment of tumor metastasis and recurrence is challenging and is associated with poor clinical efficacy. Vasculogenic mimicry (VM) is a new blood-supply model of malignant tumor that is closely related to tumors' distant metastasis. Our previous study demonstrated that miR-124 could target Foxq1 to inhibit NPC metastasis. Whether Foxq1 affects metastasis through vasculogenic mimicry is worth consideration. In this study, we show that VM formation positively correlates with the expression of Foxq1, and EGFR, and the TNM stage in 114 NPC patient samples. Meanwhile, we show that VM-positive NPC patients have a poor prognosis. Furthermore, using in vitro and vivo approaches, we confirm that Foxq1 has a significant effect on NPC metastasis through promoting VM formation, which could be effectively inhibited by EGFR inhibitors (Nimotuzumab or Erlotinib). Also a synergistic efficacy of anti-EGFR and anti-VEGF drugs has been found in NPC inhibition. Mechanistically, the luciferase reporter gene and CHIP assays show that Foxq1 directly binds to the EGFR promoter region and regulates EGFR transcription. In conclusion, our results show that Foxq1 is regulated by miR-124 and that it promotes NPC metastasis by inducing VM via the EGFR signaling pathway. Overall, these results provide a new theoretical support and a novel target selection for anti-VM therapy in the treatment of nasopharyngeal carcinoma.

• Authors: Yunfan Luo, Jie Wang, Fan Wang, Xiong Liu, Juan Lu, Xiaoxiao Yu, Xuemin Ma, Xiaohong Peng, Xiangping Li
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 5 Pg. 411 (04 19 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 33875643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXQ1 protein, human
• Forkhead Transcription Factors
• EGFR protein, human
• ErbB Receptors

Topics

• Drug Delivery Systems
• ErbB Receptors (metabolism)
• Forkhead Transcription Factors (metabolism)
• Humans
• Nasopharyngeal Carcinoma (blood supply, metabolism, pathology)
• Nasopharyngeal Neoplasms (blood supply, metabolism, pathology)
• Neoplasm Metastasis
• Signal Transduction