title: Sonic hedgehog signaling may promote invasion and metastasis of oral squamous cell carcinoma by activating MMP-9 and E-cadherin expression.
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.
authors.affiliation: Department of Anatomy, Basic Medical Science College, Harbin Medical University, 194 Xuefu-Road, Harbin, 150081, People's Republic of China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Fan
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D015820:Cadherins; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D020780:Matrix Metalloproteinase 9