Over-expression of integrin-linked kinase correlates with aberrant expression of Snail, E-cadherin and N-cadherin in oral squamous cell carcinoma: implications in tumor progression and metastasis.
Integrin-linked kinase (ILK), an intracellular protein with serine/threonine protein kinase activities, plays a key role in integrin mediated cell-excellular matrix interactions, regulating cell proliferation, apoptosis, differentiation, and migration. ILK has been implicated in the development and progression in several malignancies. However, the role of ILK and ILK-mediated epithelial-mensenchymal transition (EMT) in the progression of oral squamous cell carcinoma (OSCC) has not been well understood. Here, by immunohistochemistry, we studied the expression of ILK, Snail, E-cadherin and N-cadherin in 98 primary OSCC specimens and analyzed their correlations with clinicopathologic profiles and clinical outcome. We also investigated the expression of ILK in 42 corresponding lymph node metastases. Positive expression of ILK protein was detected in 87.8 % of the primary tumors and 100 % of metastatic lesions. Increased ILK expression was correlated strongly with enhanced tumor invasion, higher tumor grade, advanced clinical stage, positive lymph node status and increased risk of recurrence. Higher ILK expression was also observed in lymph node metastases in comparison with the corresponding primary tumor. Moreover, up-regulation of Snail and N-cadherin and down-regulation of E-cadherin correlated significantly with both ILK over-expression and tumor invasion. Patients with higher ILK expression exhibited shorter disease-free survival while those with absent E-cadherin expression exhibited shorter overall and disease-free survival. Taken together, our results suggest that ILK may have an important role in progression and metastasis of OSCC, possibly through EMT involving up-regulation of Snail and consequent aberrant expression of E-cadherin and N-cadherin. ILK should be considered as a critical prognostic indicator for patients with OSCC.
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China. zhaodan605@163.com
Dan
D
Zhao
Xiu-Fa
XF
Tang
Kai
K
Yang
Ji-Yuan
JY
Liu
Xiang-Rui
XR
Ma
D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism*; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D015820:Cadherins; D017346:Protein Serine-Threonine Kinases; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000099200:Scaffold Protein ILK