Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma.

The function of tropomyosin receptor kinase (Trk) family including TrkA, TrkB, and TrkC in cancer remains unknown. The role of Trks in oral squamous cell carcinoma (OSCC) was examined. Knockdown of Trks provided inhibition of growth or invasion and decrease of apoptosis in OSCC cells, which expressed Trks at high levels. VEGF expression was associated with TrkA and TrkB expression; a decrease of VEGF-C and VEGF-D was observed in OSCC cells with TrkB knockdown. TrkC did not affect the expression of VEGF family. An immunohistochemical analysis of 102 OSCCs showed that TrkB expression was related to microvessel density (MVD), lymph vessel density (LVD), and poor prognosis. TrkC expression was correlated with clinical stage, lymph node metastasis, MVD, LVD, and poor prognosis. TrkA expression was associated with VEGF expression, whereas TrkB expression was associated with the expressions of VEGF, VEGF-C and VEGF-D. No significant association was found between the expression of TrkC and genes of the VEGF family. Expression of Trks was not associated with RUNX3 silencing by methylation in OSCC cells. Trks expression was inversely correlated with RUNX3 expression in the OSCC cases. These results suggested that Trks enhances progression of OSCC through angiogenesis and lymphangiogenesis.