Fig. 8: A working model of LHX2-induced NPC progression.
From: LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis
LHX2 transcriptionally activates FGF1 expression. Tumour cells produce FGF1, which binds to FGFR, and the subsequent downstream signalling occurs through the intracellular receptor substrates FGFR substrate 2 (FRS2), resulting in the phosphorylation and activation of MAPK/ERK, JAK2/STAT3, and PI3K/AKT signalling pathways. (i) These pro-survival pathways are responsible for the promotion of tumour proliferation and growth. (ii) Phosphorylated AKT stimulates the Ser9-GSK3β/β-catenin signalling, leading to the EMT of NPC via the β-catenin targeted ZEB1 and TWIST1 genes and promotes tumour cell migration and invasion. (iii) FGF/FGFR trapping by AZD4547 could block the LHX2/FGF1-induced promotion on tumour growth and metastasis.
