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.

Mesenchymal Stem Cells Inhibits Migration and Vasculogenic Mimicry in Nasopharyngeal Carcinoma Via Exosomal MiR-125a

“…Evidence supports that VM structures promote tumor dissemination and metastasis ( 32 ). Furthermore, the formation of VM is strongly associated with the abnormal expression of several miRs, suggesting that miRs are potential targets for anti-VM therapy ( 9 ).…”

“…Periodic acid-Schiff (PAS) staining combining with CD34 immunohistochemistry (IHC) can be used to detect the structure of VM ( 7 ). VM has been shown to be present in various malignant tumors ( 8 ), namely, NPC ( 8 ), which is associated with tumor metastasis ( 9 ) and poor prognosis ( 7 ). Since the structure of VM is composed of cancer cells, the benefit of VEGF-targeted therapy which is focused on ECs is limited and unsatisfied.…”

Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein–Barr Virus Infection

“…The expression of these genes promotes cell cycle progression and the Warburg effect, which enhances the invasion and metastasis ability of NPC cells [72,76]. Moreover, the highly conserved transcription factors Forkhead box Q1 (Foxq1), regulated by miR-124, could directly bind to the EGFR promoter and increase EGFR expression, thereby inducing vasculogenic mimicry via the EGFR signalling pathway to promote NPC metastasis [77,78]. Similarly, the overexpression of LACTB (serine beta-lactamase-like protein) promotes NPC cell motility in vitro and metastasis in vivo, depending on the activation of ErbB3/EGFR-ERK signalling, which is not conducive to the survival of NPC patients [79].…”

Cross‑link between ferroptosis and nasopharyngeal carcinoma: New approach to radiotherapy sensitization (Review)

“…Deng et al ( 113 ) suggested that miR-124 was able to radiosensitize glioblastoma multiforme cells by targeting CDK4. In addition, miR-124 has been reported to be downregulated in NPC ( 114 ). miR-124 may enhance cell radiosensitivity by targeting JAMA and PDCD6 ( 105 ).…”