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.
Highlights
Nasopharyngeal carcinoma is a malignant tumor that has a high incidence in Southeast Asia, especially in southern China
As epidermal growth factor receptor (EGFR) has been reported as an important regulator of Vasculogenic mimicry (VM) in various malignancies[30,31], we considered that VM may be the main leading cause that is associated with the difference in efficacy of anti-angiogenic drugs and anti-EGFR drugs in nasopharyngeal carcinoma
Foxq1-EGFR axis contributes to nasopharyngeal carcinoma (NPC) growth and metastasis through regulating VM formation
Summary
Nasopharyngeal carcinoma is a malignant tumor that has a high incidence in Southeast Asia, especially in southern China. Recurrence or distant metastasis is still the biggest challenge in the treatment of nasopharyngeal carcinoma, and the main cause of patients’ death[3]. Clarifying the Angiogenesis is an essential process of malignant tumors’ growth and metastasis[4]. Angiogenesis was believed to be the only blood-supply model for tumors; anti-angiogenic therapy was considered as an effective treatment for preventing metastasis. Anti-angiogenic drugs mainly target the VEGF/ VEGFR signaling pathway, anti-VEGF drugs have not achieved certain clinical effects in the treatment of nasopharyngeal carcinoma[5,6]. It is important to investigate the causes that are associated with the poor efficacy of anti-angiogenic drugs in nasopharyngeal carcinoma
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
