title: Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ueda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Miyako
authors.initials: M
authors.lastname: Kurihara
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D050677:Core Binding Factor Alpha 3 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050677:Core Binding Factor Alpha 3 Subunit; D034741:RNA, Small Interfering; C493729:Runx3 protein, human; D004247:DNA; D020917:Receptor, trkA