Skip to main content

01.02.2013 | Research Paper

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

verfasst von: Tomonori Sasahira, Nobuhiro Ueda, Kazuhiko Yamamoto, Ujjal K. Bhawal, Miyako Kurihara, Tadaaki Kirita, Hiroki Kuniyasu

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 2/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Chen YJ, Lin SC, Kao T, Chang CS, Hong PS, Shieh TM, Chang KW (2004) Genome-wide profiling of oral squamous cell carcinoma. J Pathol 204:326–332PubMedCrossRef Chen YJ, Lin SC, Kao T, Chang CS, Hong PS, Shieh TM, Chang KW (2004) Genome-wide profiling of oral squamous cell carcinoma. J Pathol 204:326–332PubMedCrossRef
2.
Zurück zum Zitat Hunter KD, Parkinson EK, Harrison PR (2005) Profiling early head and neck cancer. Nat Rev Cancer 5:127–135PubMedCrossRef Hunter KD, Parkinson EK, Harrison PR (2005) Profiling early head and neck cancer. Nat Rev Cancer 5:127–135PubMedCrossRef
3.
Zurück zum Zitat Lippman SM, Hong WK (2001) Molecular markers of the risk of oral cancer. N Engl J Med 344:1323–1326PubMedCrossRef Lippman SM, Hong WK (2001) Molecular markers of the risk of oral cancer. N Engl J Med 344:1323–1326PubMedCrossRef
4.
Zurück zum Zitat Tanaka S, Sobue T (2005) Comparison of oral and pharyngeal cancer mortality in five countries: France, Italy, Japan, UK and USA from the WHO Mortality Database (1960–2000). Jpn J Clin Oncol 35:488–491PubMedCrossRef Tanaka S, Sobue T (2005) Comparison of oral and pharyngeal cancer mortality in five countries: France, Italy, Japan, UK and USA from the WHO Mortality Database (1960–2000). Jpn J Clin Oncol 35:488–491PubMedCrossRef
5.
Zurück zum Zitat Hershkovich O, Oliva J, Nagler RM (2004) Lethal synergistic effect of cigarette smoke and saliva in an in vitro model: does saliva have a role in the development of oral cancer? Eur J Cancer 40:1760–1767PubMedCrossRef Hershkovich O, Oliva J, Nagler RM (2004) Lethal synergistic effect of cigarette smoke and saliva in an in vitro model: does saliva have a role in the development of oral cancer? Eur J Cancer 40:1760–1767PubMedCrossRef
6.
Zurück zum Zitat Dos Reis PP, Bharadwaj RR, Machado J, Macmillan C, Pintilie M, Sukhai MA, Perez-Ordonez B, Gullane P, Irish J, Kamel-Reid S (2008) Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma. Cancer 113:3169–3180PubMedCrossRef Dos Reis PP, Bharadwaj RR, Machado J, Macmillan C, Pintilie M, Sukhai MA, Perez-Ordonez B, Gullane P, Irish J, Kamel-Reid S (2008) Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma. Cancer 113:3169–3180PubMedCrossRef
7.
Zurück zum Zitat Thiele CJ, Li Z, McKee AE (2009) On Trk: the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin Cancer Res 15:5962–5967PubMedCrossRef Thiele CJ, Li Z, McKee AE (2009) On Trk: the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin Cancer Res 15:5962–5967PubMedCrossRef
8.
Zurück zum Zitat Inoue K, Ito K, Osato M, Lee B, Bae SC, Ito Y (2007) The transcription factor Runx3 represses the neurotrophin receptor TrkB during lineage commitment of dorsal root ganglion neurons. J Biol Chem 282:24175–24184PubMedCrossRef Inoue K, Ito K, Osato M, Lee B, Bae SC, Ito Y (2007) The transcription factor Runx3 represses the neurotrophin receptor TrkB during lineage commitment of dorsal root ganglion neurons. J Biol Chem 282:24175–24184PubMedCrossRef
9.
Zurück zum Zitat Nakamura S, Senzaki K, Yoshikawa M, Nishimura M, Inoue K, Ito Y, Ozaki S, Shiga T (2008) Dynamic regulation of the expression of neurotrophin receptors by Runx3. Development 135:1703–1711PubMedCrossRef Nakamura S, Senzaki K, Yoshikawa M, Nishimura M, Inoue K, Ito Y, Ozaki S, Shiga T (2008) Dynamic regulation of the expression of neurotrophin receptors by Runx3. Development 135:1703–1711PubMedCrossRef
10.
Zurück zum Zitat Sasahira T, Kurihara M, Yamamoto K, Bhawal U, Kirita T, Kuniyasu H (2011) Downregulation of runt-related transcription factor 3 (RUNX3) associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland. Cancer Sci 102:492–497PubMedCrossRef Sasahira T, Kurihara M, Yamamoto K, Bhawal U, Kirita T, Kuniyasu H (2011) Downregulation of runt-related transcription factor 3 (RUNX3) associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland. Cancer Sci 102:492–497PubMedCrossRef
11.
Zurück zum Zitat Tessarollo L (1998) Pleiotropic functions of neurotrophins in development. Cytokine Growth Factor Rev 9:125–137PubMedCrossRef Tessarollo L (1998) Pleiotropic functions of neurotrophins in development. Cytokine Growth Factor Rev 9:125–137PubMedCrossRef
12.
Zurück zum Zitat Yu X, Liu L, Cai B, He Y, Wan X (2008) Suppression of anoikis by the neurotrophic receptor TrkB in human ovarian cancer. Cancer Sci 99:543–552PubMedCrossRef Yu X, Liu L, Cai B, He Y, Wan X (2008) Suppression of anoikis by the neurotrophic receptor TrkB in human ovarian cancer. Cancer Sci 99:543–552PubMedCrossRef
13.
Zurück zum Zitat Bouzas-Rodriguez J, Cabrera JR, Delloye-Bourgeois C, Ichim G, Delcros JG, Raquin MA, Rousseau R, Combaret V, Bénard J, Tauszig-Delamasure S, Mehlen P (2010) Neurotrophin-3 production promotes human neuroblastoma cell survival by inhibiting TrkC-induced apoptosis. J Clin Invest 120:850–858PubMedCrossRef Bouzas-Rodriguez J, Cabrera JR, Delloye-Bourgeois C, Ichim G, Delcros JG, Raquin MA, Rousseau R, Combaret V, Bénard J, Tauszig-Delamasure S, Mehlen P (2010) Neurotrophin-3 production promotes human neuroblastoma cell survival by inhibiting TrkC-induced apoptosis. J Clin Invest 120:850–858PubMedCrossRef
14.
Zurück zum Zitat Davidson B, Reich R, Lazarovici P, Nesland JM, Skrede M, Risberg B, Tropé CG, Flørenes VA (2003) Expression and activation of the nerve growth factor receptor TrkA in serous ovarian carcinoma. Clin Cancer Res 9:2248–2259PubMed Davidson B, Reich R, Lazarovici P, Nesland JM, Skrede M, Risberg B, Tropé CG, Flørenes VA (2003) Expression and activation of the nerve growth factor receptor TrkA in serous ovarian carcinoma. Clin Cancer Res 9:2248–2259PubMed
15.
Zurück zum Zitat Sclabas GM, Fujioka S, Schmidt C, Li Z, Frederick WA, Yang W, Yokoi K, Evans DB, Abbruzzese JL, Hess KR, Zhang W, Fidler IJ, Chiao PJ (2005) Overexpression of tropomysin-related kinase B in metastatic human pancreatic cancer cells. Clin Cancer Res 11:440–449PubMed Sclabas GM, Fujioka S, Schmidt C, Li Z, Frederick WA, Yang W, Yokoi K, Evans DB, Abbruzzese JL, Hess KR, Zhang W, Fidler IJ, Chiao PJ (2005) Overexpression of tropomysin-related kinase B in metastatic human pancreatic cancer cells. Clin Cancer Res 11:440–449PubMed
16.
Zurück zum Zitat Yang ZF, Ho DW, Lam CT, Luk JM, Lum CT, Yu WC, Poon RT, Fan ST (2005) Identification of brain-derived neurotrophic factor as a novel functional protein in hepatocellular carcinoma. Cancer Res 65:219–225PubMed Yang ZF, Ho DW, Lam CT, Luk JM, Lum CT, Yu WC, Poon RT, Fan ST (2005) Identification of brain-derived neurotrophic factor as a novel functional protein in hepatocellular carcinoma. Cancer Res 65:219–225PubMed
17.
Zurück zum Zitat Satoh F, Mimata H, Nomura T, Fujita Y, Shin T, Sakamoto S, Hamada Y, Nomura Y (2001) Autocrine expression of neurotrophins and their receptors in prostate cancer. Int J Urol 8:S28–S34PubMedCrossRef Satoh F, Mimata H, Nomura T, Fujita Y, Shin T, Sakamoto S, Hamada Y, Nomura Y (2001) Autocrine expression of neurotrophins and their receptors in prostate cancer. Int J Urol 8:S28–S34PubMedCrossRef
18.
Zurück zum Zitat Nakagawara A, Azar CG, Scavarda NJ, Brodeur GM (1994) Expression and function of TRK-B and BDNF in human neuroblastomas. Mol Cell Biol 14:759–767PubMed Nakagawara A, Azar CG, Scavarda NJ, Brodeur GM (1994) Expression and function of TRK-B and BDNF in human neuroblastomas. Mol Cell Biol 14:759–767PubMed
19.
Zurück zum Zitat Chen-Tsai CP, Colome-Grimmer M, Wagner RF Jr (2004) Correlations among neural cell adhesion molecule, nerve growth factor, and its receptors, TrkA, TrkB, TrkC, and p75, in perineural invasion by basal cell and cutaneous squamous cell carcinomas. Dermatol Surg 30:1009–1016PubMedCrossRef Chen-Tsai CP, Colome-Grimmer M, Wagner RF Jr (2004) Correlations among neural cell adhesion molecule, nerve growth factor, and its receptors, TrkA, TrkB, TrkC, and p75, in perineural invasion by basal cell and cutaneous squamous cell carcinomas. Dermatol Surg 30:1009–1016PubMedCrossRef
20.
Zurück zum Zitat Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB, Brodeur GM (1993) Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. N Engl J Med 328:847–854PubMedCrossRef Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB, Brodeur GM (1993) Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. N Engl J Med 328:847–854PubMedCrossRef
21.
Zurück zum Zitat Yamashiro DJ, Nakagawara A, Ikegaki N, Liu XG, Brodeur GM (1996) Expression of TrkC in favorable human neuroblastomas. Oncogene 12:37–41PubMed Yamashiro DJ, Nakagawara A, Ikegaki N, Liu XG, Brodeur GM (1996) Expression of TrkC in favorable human neuroblastomas. Oncogene 12:37–41PubMed
22.
Zurück zum Zitat Segal RA, Goumnerova LC, Kwon YK, Stiles CD, Pomeroy SL (1994) Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc Natl Acad Sci USA 91:12867–12871PubMedCrossRef Segal RA, Goumnerova LC, Kwon YK, Stiles CD, Pomeroy SL (1994) Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc Natl Acad Sci USA 91:12867–12871PubMedCrossRef
23.
Zurück zum Zitat Sasahira T, Oue N, Kirita T, Luo Y, Bhawal UK, Fujii K, Yasui W, Kuniyasu H (2008) Reg IV expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland. Histopathology 53:667–675PubMedCrossRef Sasahira T, Oue N, Kirita T, Luo Y, Bhawal UK, Fujii K, Yasui W, Kuniyasu H (2008) Reg IV expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland. Histopathology 53:667–675PubMedCrossRef
24.
Zurück zum Zitat Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y (2002) Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 109:113–124PubMedCrossRef Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y (2002) Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 109:113–124PubMedCrossRef
25.
Zurück zum Zitat Sasaki T, Fujii K, Yoshida K, Shimura H, Sasahira T, Ohmori H, Kuniyasu H (2006) Peritoneal metastasis inhibition by linoleic acid with activation of PPARγ in human gastrointestinal cancer cells. Virchows Arch 448:422–427PubMedCrossRef Sasaki T, Fujii K, Yoshida K, Shimura H, Sasahira T, Ohmori H, Kuniyasu H (2006) Peritoneal metastasis inhibition by linoleic acid with activation of PPARγ in human gastrointestinal cancer cells. Virchows Arch 448:422–427PubMedCrossRef
26.
Zurück zum Zitat Sasaki T, Shimura H, Sasahira T, Fujii K, Kuniyasu H (2005) High concentration of deoxycholic acid abrogates in vitro transformation of IEC6 intestinal cells by azoxymethane. J Exp Clin Cancer Res 24:625–631PubMed Sasaki T, Shimura H, Sasahira T, Fujii K, Kuniyasu H (2005) High concentration of deoxycholic acid abrogates in vitro transformation of IEC6 intestinal cells by azoxymethane. J Exp Clin Cancer Res 24:625–631PubMed
27.
Zurück zum Zitat Sasahira T, Akama Y, Fujii K, Kuniyasu H (2005) Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas. Virchows Arch 446:411–415PubMedCrossRef Sasahira T, Akama Y, Fujii K, Kuniyasu H (2005) Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas. Virchows Arch 446:411–415PubMedCrossRef
28.
Zurück zum Zitat Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed
29.
Zurück zum Zitat Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, Yasui W, Kuniyasu H (2008) High mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. Cancer Sci 99:1806–1812PubMed Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, Yasui W, Kuniyasu H (2008) High mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. Cancer Sci 99:1806–1812PubMed
30.
Zurück zum Zitat Sasahira T, Kirita T, Bhawal UK, Ikeda M, Nagasawa A, Yamamoto K, Kuniyasu H (2007) The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma. Virchows Arch 450:287–295PubMedCrossRef Sasahira T, Kirita T, Bhawal UK, Ikeda M, Nagasawa A, Yamamoto K, Kuniyasu H (2007) The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma. Virchows Arch 450:287–295PubMedCrossRef
31.
Zurück zum Zitat Sasahira T, Kirita T, Kurihara M, Yamamoto K, Bhawal UK, Bosserhoff AK, Kuniyasu H (2010) MIA-dependent angiogenesis and lymphangiogenesis are closely associated with progression, nodal metastasis and poor prognosis in tongue squamous cell carcinoma. Eur J Cancer 46:2285–2294PubMedCrossRef Sasahira T, Kirita T, Kurihara M, Yamamoto K, Bhawal UK, Bosserhoff AK, Kuniyasu H (2010) MIA-dependent angiogenesis and lymphangiogenesis are closely associated with progression, nodal metastasis and poor prognosis in tongue squamous cell carcinoma. Eur J Cancer 46:2285–2294PubMedCrossRef
32.
Zurück zum Zitat Nakamura K, Martin KC, Jackson JK, Beppu K, Woo CW, Thiele CJ (2006) Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res 66:4249–4255PubMedCrossRef Nakamura K, Martin KC, Jackson JK, Beppu K, Woo CW, Thiele CJ (2006) Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res 66:4249–4255PubMedCrossRef
33.
Zurück zum Zitat Tacconelli A, Farina AR, Cappabianca L, Desantis G, Tessitore A, Vetuschi A, Sferra R, Rucci N, Argenti B, Screpanti I, Gulino A, Mackay AR (2004) TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell 6:347–360PubMedCrossRef Tacconelli A, Farina AR, Cappabianca L, Desantis G, Tessitore A, Vetuschi A, Sferra R, Rucci N, Argenti B, Screpanti I, Gulino A, Mackay AR (2004) TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell 6:347–360PubMedCrossRef
34.
Zurück zum Zitat Cristofaro B, Stone OA, Caporali A, Dawbarn D, Ieronimakis N, Reyes M, Madeddu P, Bates DO, Emanueli C (2010) Neurotrophin-3 is a novel angiogenic factor capable of therapeutic neovascularization in a mouse model of limb ischemia. Arterioscler Thromb Vasc Biol 30:1143–1150PubMedCrossRef Cristofaro B, Stone OA, Caporali A, Dawbarn D, Ieronimakis N, Reyes M, Madeddu P, Bates DO, Emanueli C (2010) Neurotrophin-3 is a novel angiogenic factor capable of therapeutic neovascularization in a mouse model of limb ischemia. Arterioscler Thromb Vasc Biol 30:1143–1150PubMedCrossRef
35.
Zurück zum Zitat Brzezianska E, Pastuszak-Lewandoska D, Lewinski A (2007) Rearrangements of NTRK1 oncogene in papillary thyroid carcinoma. Neuro Endocrinol Lett 28:221–229PubMed Brzezianska E, Pastuszak-Lewandoska D, Lewinski A (2007) Rearrangements of NTRK1 oncogene in papillary thyroid carcinoma. Neuro Endocrinol Lett 28:221–229PubMed
36.
Zurück zum Zitat McGregor LM, McCune BK, Graff JR, McDowell PR, Romans KE, Yancopoulos GD, Ball DW, Baylin SB, Nelkin BD (1999) Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression. Proc Natl Acad Sci USA 96:4540–4545PubMedCrossRef McGregor LM, McCune BK, Graff JR, McDowell PR, Romans KE, Yancopoulos GD, Ball DW, Baylin SB, Nelkin BD (1999) Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression. Proc Natl Acad Sci USA 96:4540–4545PubMedCrossRef
37.
Zurück zum Zitat Riedel F, Gotte K, Bergler W, Hormann K (2001) Inverse correlation of apoptotic and angiogenic markers in squamous cell carcinoma of the head and neck. Oncol Rep 8:471–476PubMed Riedel F, Gotte K, Bergler W, Hormann K (2001) Inverse correlation of apoptotic and angiogenic markers in squamous cell carcinoma of the head and neck. Oncol Rep 8:471–476PubMed
38.
Zurück zum Zitat Larcher F, Robles AI, Duran H, Murillas R, Quintanilla M, Cano A, Conti CJ, Jorcano JL (1996) Up-regulation of vascular endothelial growth factor/vascular permeability factor in mouse skin carcinogenesis correlates with malignant progression state and activated H-ras expression levels. Cancer Res 56:5391–5396PubMed Larcher F, Robles AI, Duran H, Murillas R, Quintanilla M, Cano A, Conti CJ, Jorcano JL (1996) Up-regulation of vascular endothelial growth factor/vascular permeability factor in mouse skin carcinogenesis correlates with malignant progression state and activated H-ras expression levels. Cancer Res 56:5391–5396PubMed
39.
Zurück zum Zitat Li Z, Jaboin J, Dennis PA, Thiele CJ (2005) Genetic and pharmacologic identification of Akt as a mediator of brain-derived neurotrophic factor/TrkB rescue of neuroblastoma cells from chemotherapy-induced cell death. Cancer Res 65:2070–2075PubMedCrossRef Li Z, Jaboin J, Dennis PA, Thiele CJ (2005) Genetic and pharmacologic identification of Akt as a mediator of brain-derived neurotrophic factor/TrkB rescue of neuroblastoma cells from chemotherapy-induced cell death. Cancer Res 65:2070–2075PubMedCrossRef
40.
Zurück zum Zitat Jin W, Yun C, Kwak MK, Kim TA, Kim SJ (2007) TrkC binds to the type II TGF-beta receptor to suppress TGF-beta signaling. Oncogene 26:7684–7691PubMedCrossRef Jin W, Yun C, Kwak MK, Kim TA, Kim SJ (2007) TrkC binds to the type II TGF-beta receptor to suppress TGF-beta signaling. Oncogene 26:7684–7691PubMedCrossRef
41.
Zurück zum Zitat Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, Stavnezer J, Kawabata M, Miyazono K, Ito Y (1999) Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter. J Biol Chem 274:31577–31582PubMedCrossRef Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, Stavnezer J, Kawabata M, Miyazono K, Ito Y (1999) Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter. J Biol Chem 274:31577–31582PubMedCrossRef
42.
Zurück zum Zitat Zaidi SK, Sullivan AJ, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2002) Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci USA 99:8048–8053PubMedCrossRef Zaidi SK, Sullivan AJ, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2002) Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci USA 99:8048–8053PubMedCrossRef
43.
Zurück zum Zitat Chuang LS, Ito Y (2010) RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. Oncogene 9:2605–2615CrossRef Chuang LS, Ito Y (2010) RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. Oncogene 9:2605–2615CrossRef
44.
Zurück zum Zitat Tsunematsu T, Kudo Y, Iizuka S, Ogawa I, Fujita T, Kurihara H, Abiko Y, Takata T (2009) RUNX3 has an oncogenic role in head and neck cancer. PLoS ONE 4:e5892PubMedCrossRef Tsunematsu T, Kudo Y, Iizuka S, Ogawa I, Fujita T, Kurihara H, Abiko Y, Takata T (2009) RUNX3 has an oncogenic role in head and neck cancer. PLoS ONE 4:e5892PubMedCrossRef
45.
Zurück zum Zitat Jain RK, Munn LL, Fukumura D (2002) Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 2:266–276PubMedCrossRef Jain RK, Munn LL, Fukumura D (2002) Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 2:266–276PubMedCrossRef
46.
Zurück zum Zitat Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62PubMedCrossRef Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62PubMedCrossRef
Metadaten
Titel
Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma
verfasst von
Tomonori Sasahira
Nobuhiro Ueda
Kazuhiko Yamamoto
Ujjal K. Bhawal
Miyako Kurihara
Tadaaki Kirita
Hiroki Kuniyasu
Publikationsdatum
01.02.2013
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 2/2013
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-012-9525-x

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.