Skip to main content
Erschienen in: Medical Oncology 7/2014

01.07.2014 | Original Paper

Sonic hedgehog signaling may promote invasion and metastasis of oral squamous cell carcinoma by activating MMP-9 and E-cadherin expression

verfasst von: Hai-Xia Fan, Shan Wang, Hong Zhao, Nian Liu, Dong Chen, Miao Sun, Jin-Hua Zheng

Erschienen in: Medical Oncology | Ausgabe 7/2014

Einloggen, um Zugang zu erhalten

Abstract

The aim of this study was to investigate sonic hedgehog (SHH) signaling pathway components (Shh and Gli-1), E-cadherin, and MMP-9 expression in human oral squamous cell carcinoma (OSCC) and to evaluate their role in prognosis. Expression of Shh, Gli-1, and MMP-9 was significantly upregulated in 74 OSCC samples compared with non-cancerous tissue samples (Shh IOD: 162.44 ± 29.35 and 608.82 ± 170.99; Gli-1 IOD: 203.50 ± 71.57 and 831.11 ± 242.352; MMP-9 IOD: 196.69 ± 64.48 and 721.64 ± 197.99 in non-cancerous and tumor tissues, respectively, P < 0.01), whereas E-cadherin expression was downregulated (E-cadherin IOD: 1,006.19 ± 230.42 and 442.20 ± 156.11; in non-cancerous and tumor tissues, respectively, P < 0.01). Highly expressed proteins were associated with lymph node metastasis; moreover, overexpression of Gli-1 was related to tumor recurrence and cancer clinical staging. Spearman’s analysis indicated that the expression of Gli-1 and MMP-9 was positively correlated, whereas expression of Shh/Gli-1 and E-cadherin was negatively correlated. Kaplan–Meier results revealed that patients with low Shh, Gli-1, and MMP-9 expression survived longer than those with high expression. In contrast, low E-cadherin expression was associated with poor prognosis (P < 0.01). In conclusions, transcription factor Gli-1 of the SHH signaling pathway may be an important mediator of invasion and metastasis of OSCC through induced expression of MMP-9 and E-cadherin and may serve as a new prognostic marker.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Byers RM, El-Naggar AK, Lee YY, Rao B, Fornage B, Terry NH, et al. Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue? Head Neck. 1998;20(2):138–44.PubMedCrossRef Byers RM, El-Naggar AK, Lee YY, Rao B, Fornage B, Terry NH, et al. Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue? Head Neck. 1998;20(2):138–44.PubMedCrossRef
3.
Zurück zum Zitat Yoo YA, Kang MH, Lee HJ, Kim BH, Park JK, Kim HK, et al. Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res. 2011;71(22):7061–70. doi:10.1158/0008-5472.CAN-11-1338.PubMedCrossRef Yoo YA, Kang MH, Lee HJ, Kim BH, Park JK, Kim HK, et al. Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res. 2011;71(22):7061–70. doi:10.​1158/​0008-5472.​CAN-11-1338.PubMedCrossRef
4.
Zurück zum Zitat Chen JS, Huang XH, Wang Q, Huang JQ, Zhang LJ, Chen XL, et al. Sonic hedgehog signaling pathway induces cell migration and invasion through focal adhesion kinase/AKT signaling-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9 in liver cancer. Carcinogenesis. 2013;34(1):10–9. doi:10.1093/carcin/bgs274.PubMedCrossRef Chen JS, Huang XH, Wang Q, Huang JQ, Zhang LJ, Chen XL, et al. Sonic hedgehog signaling pathway induces cell migration and invasion through focal adhesion kinase/AKT signaling-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9 in liver cancer. Carcinogenesis. 2013;34(1):10–9. doi:10.​1093/​carcin/​bgs274.PubMedCrossRef
6.
Zurück zum Zitat Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009;361(12):1164–72. doi:10.1056/NEJMoa0905360.CrossRef Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009;361(12):1164–72. doi:10.​1056/​NEJMoa0905360.CrossRef
7.
Zurück zum Zitat Wang YF, Chang CJ, Lin CP, Chang SY, Chu PY, Tai SK, et al. Expression of hedgehog signaling molecules as a prognostic indicator of oral squamous cell carcinoma. Head Neck. 2012;34(11):1556–61. doi:10.1002/hed.21958.PubMedCrossRef Wang YF, Chang CJ, Lin CP, Chang SY, Chu PY, Tai SK, et al. Expression of hedgehog signaling molecules as a prognostic indicator of oral squamous cell carcinoma. Head Neck. 2012;34(11):1556–61. doi:10.​1002/​hed.​21958.PubMedCrossRef
12.
Zurück zum Zitat Tian T, Nan KJ, Guo H, Wang WJ, Ruan ZP, Wang SH, et al. PTEN inhibits the migration and invasion of HepG2 cells by coordinately decreasing MMP expression via the PI3K/Akt pathway. Oncol Rep. 2010;23(6):1593–600.PubMed Tian T, Nan KJ, Guo H, Wang WJ, Ruan ZP, Wang SH, et al. PTEN inhibits the migration and invasion of HepG2 cells by coordinately decreasing MMP expression via the PI3K/Akt pathway. Oncol Rep. 2010;23(6):1593–600.PubMed
17.
Zurück zum Zitat Katoh Y, Katoh M. Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA (review). Int J Mol Med. 2008;22(3):271–5.PubMed Katoh Y, Katoh M. Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA (review). Int J Mol Med. 2008;22(3):271–5.PubMed
20.
Zurück zum Zitat Akdeniz O, Akduman D, Haksever M, Ozkarakas H, Muezzinoglu B. Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, mmp-9 and e-cadherin. Asian Pac J Cancer Prev. 2013;14(9):5301–10.PubMedCrossRef Akdeniz O, Akduman D, Haksever M, Ozkarakas H, Muezzinoglu B. Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, mmp-9 and e-cadherin. Asian Pac J Cancer Prev. 2013;14(9):5301–10.PubMedCrossRef
23.
Zurück zum Zitat Leovic D, Sabol M, Ozretic P, Musani V, Car D, Marjanovic K, et al. Hh-Gli signaling pathway activity in oral and oropharyngeal squamous cell carcinoma. Head Neck. 2012;34(1):104–12. doi:10.1002/hed.21696.PubMedCrossRef Leovic D, Sabol M, Ozretic P, Musani V, Car D, Marjanovic K, et al. Hh-Gli signaling pathway activity in oral and oropharyngeal squamous cell carcinoma. Head Neck. 2012;34(1):104–12. doi:10.​1002/​hed.​21696.PubMedCrossRef
25.
26.
Zurück zum Zitat Asai J, Takenaka H, Kusano KF, Ii M, Luedemann C, Curry C, et al. Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling. Circulation. 2006;113(20):2413–24. doi:10.1161/CIRCULATIONAHA.105.603167.PubMedCrossRef Asai J, Takenaka H, Kusano KF, Ii M, Luedemann C, Curry C, et al. Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling. Circulation. 2006;113(20):2413–24. doi:10.​1161/​CIRCULATIONAHA.​105.​603167.PubMedCrossRef
29.
Zurück zum Zitat Matsumura T, Makino R, Mitamura K. Frequent down-regulation of E-cadherin by genetic and epigenetic changes in the malignant progression of hepatocellular carcinomas. Clin Cancer Res. 2001;7(3):594–9.PubMed Matsumura T, Makino R, Mitamura K. Frequent down-regulation of E-cadherin by genetic and epigenetic changes in the malignant progression of hepatocellular carcinomas. Clin Cancer Res. 2001;7(3):594–9.PubMed
31.
Zurück zum Zitat Reddy P, Liu L, Ren C, Lindgren P, Boman K, Shen Y, et al. Formation of E-cadherin-mediated cell–cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells. Mol Endocrinol. 2005;19(10):2564–78. doi:10.1210/me.2004-0342.PubMedCrossRef Reddy P, Liu L, Ren C, Lindgren P, Boman K, Shen Y, et al. Formation of E-cadherin-mediated cell–cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells. Mol Endocrinol. 2005;19(10):2564–78. doi:10.​1210/​me.​2004-0342.PubMedCrossRef
34.
Zurück zum Zitat Fan CC, Wang TY, Cheng YA, Jiang SS, Cheng CW, Lee AY, et al. Expression of E-cadherin, Twist, and p53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol. 2013;139(10):1735–44. doi:10.1007/s00432-013-1499-9.PubMedCrossRef Fan CC, Wang TY, Cheng YA, Jiang SS, Cheng CW, Lee AY, et al. Expression of E-cadherin, Twist, and p53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol. 2013;139(10):1735–44. doi:10.​1007/​s00432-013-1499-9.PubMedCrossRef
36.
Zurück zum Zitat Wang ZS, Shen Y, Li X, Zhou CZ, Wen YG, Jin YB et al. Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer. Tumour Biol. 2013. doi:10.1007/s13277-013-1185-1. Wang ZS, Shen Y, Li X, Zhou CZ, Wen YG, Jin YB et al. Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer. Tumour Biol. 2013. doi:10.​1007/​s13277-013-1185-1.
38.
Zurück zum Zitat Bai CB, Auerbach W, Lee JS, Stephen D, Joyner AL. Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development. 2002;129(20):4753–61.PubMed Bai CB, Auerbach W, Lee JS, Stephen D, Joyner AL. Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development. 2002;129(20):4753–61.PubMed
Metadaten
Titel
Sonic hedgehog signaling may promote invasion and metastasis of oral squamous cell carcinoma by activating MMP-9 and E-cadherin expression
verfasst von
Hai-Xia Fan
Shan Wang
Hong Zhao
Nian Liu
Dong Chen
Miao Sun
Jin-Hua Zheng
Publikationsdatum
01.07.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 7/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0041-5

Weitere Artikel der Ausgabe 7/2014

Medical Oncology 7/2014 Zur Ausgabe

Update Onkologie

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