ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway.
Integrin-linked kinase (ILK) has been implicated in the development and progression of several human malignancies. However, the role of ILK in human colon cancer progression is not well established, neither have its possible in vivo downstream effectors in the disease been identified. We studied, by immunohistochemistry, ILK, beta-catenin, E-cadherin, p-Akt and p-FKHR protein expression in 125 primary colon carcinomas and 45 corresponding lymph node metastases. ILK was expressed in 98.4% of the primary tumours and in 100% of metastatic lesions. The levels of ILK expression correlated strongly with tumour invasion, tumour grade and stage and were significantly higher in metastatic tumours. Activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway correlated significantly with both ILK expression and tumour progression parameters. In conclusion, our results suggest that ILK may have an important role in progression of human colon cancer, possibly through in vivo regulation of beta-catenin, E-cadherin and Akt pathways. Our study also provides some evidence implicating p-FKHR in human colon carcinogenesis and ILK signalling.
Bravou
V
V
Department of Anatomy, School of Medicine, University of Patras, 26500 Rio Patras, Greece.
Klironomos
G
G
Papadaki
E
E
Taraviras
S
S
Varakis
J
J
D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D009367:Neoplasm Staging; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism*; D051176:beta Catenin / Q000032:analysis / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D015820:Cadherins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C085126:FOXO1 protein, human