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

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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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (305400083).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Anatomy, Basic Medical Science College, Harbin Medical University, 194 Xuefu-Road, Harbin, 150081, People’s Republic of China

    Hai-Xia Fan, Shan Wang, Hong Zhao, Nian Liu & Jin-Hua Zheng

  2. Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Harbin Medical University, Harbin, 150001, People’s Republic of China

    Dong Chen & Miao Sun

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  1. Hai-Xia Fan
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Fan, HX., Wang, S., Zhao, H. et al. Sonic hedgehog signaling may promote invasion and metastasis of oral squamous cell carcinoma by activating MMP-9 and E-cadherin expression. Med Oncol 31, 41 (2014). https://doi.org/10.1007/s12032-014-0041-5

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