LHX2 Facilitates the Progression of Nasopharyngeal Carcinoma via Activation of the FGF1/FGFR Axis

Abstract

Distant metastasis and recurrence remain the main obstacle for nasopharyngeal carcinoma (NPC) treatment. However, the molecular mechanisms underlying NPC growth and metastasis are poorly understood. We identified LIM-homeodomain transcription factor 2 (LHX2) was upregulated in NPC tissues and cell lines. Elevated LHX2 was closely associated with poor survival in NPC patients. Ectopic LHX2 expression dramatically promoted the growth, migration and invasion of NPC cells both in vitr o and in vivo . Mechanistically, LHX2 transcriptionally increased the Fibroblast Growth Factor 1 (FGF1) expression, which in turn activated the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3), ERK1/2 (Extracellular Regulated Protein Kinases 1/2) and AKT signaling pathways in an autocrine and paracrine manner, thereby promoting the growth and metastasis of NPC. Inhibition of FGF1 with a neutralizing antibody or FGFR inhibitor blocked LHX2-induced nasopharyngeal carcinoma cell growth, migration and invasion. Overall, our study identifies the LHX2-FGF1-FGFR axis plays a key role in NPC progression, and provides a potential target for NPC therapy. Funding: This work was supported by National Natural Science Foundation of China (grant numbers: 81773354), the National Natural Science Foundation of China (grant numbers: 81872195), the National Natural Science Foundation of China (grant numbers: 82003212) and Guangzhou Key Medical Discipline Construction Project Fund. Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: Our study has been approved by the Institutional Ethical Review Board of the Affiliated Cancer Hospital and Institute of Guangzhou Medical University.