Medical Oncology

, 31:41 | Cite as

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

  • Hai-Xia Fan
  • Shan Wang
  • Hong Zhao
  • Nian Liu
  • Dong Chen
  • Miao Sun
  • Jin-Hua Zheng
Original Paper

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.

Keywords

Oral squamous cell carcinoma Sonic hedgehog signaling MMP-9 E-cadherin Immunohistochemistry Prognosis 

Supplementary material

12032_2014_41_MOESM1_ESM.ppt (2.8 mb)
Supplementary material 1 (PPT 2831 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hai-Xia Fan
    • 1
  • Shan Wang
    • 1
  • Hong Zhao
    • 1
  • Nian Liu
    • 1
  • Dong Chen
    • 2
  • Miao Sun
    • 2
  • Jin-Hua Zheng
    • 1
  1. 1.Department of Anatomy, Basic Medical Science CollegeHarbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of Oral and Maxillofacial Surgery, Stomatological HospitalHarbin Medical UniversityHarbinPeople’s Republic of China

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