Cancer Cell Biology
Osteonectin downregulates E-cadherin, induces Osteopontin and Focal adhesion kinase activity stimulating an invasive melanoma phenotype
Article first published online: 27 AUG 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 12, pages 2653–2660, 15 December 2007
How to Cite
Smit, D. J., Gardiner, B. B. and Sturm, R. A. (2007), Osteonectin downregulates E-cadherin, induces Osteopontin and Focal adhesion kinase activity stimulating an invasive melanoma phenotype. Int. J. Cancer, 121: 2653–2660. doi: 10.1002/ijc.23039
- Issue published online: 22 OCT 2007
- Article first published online: 27 AUG 2007
- Manuscript Accepted: 26 JUN 2007
- Manuscript Received: 18 DEC 2006
- National Health and Medical Research Council of Australia. Grant Number: NHMRC-102565
- Queensland Cancer Fund (QCF)
- Focal adhesion kinase;
Osteonectin is recognised as a marker of metastasis progression in melanoma and has been implicated in the transition from radial to vertical growth phase. A Tetracycline-inducible system was used to regulate Osteonectin protein levels in melanoma cell lines to examine the morphological, biochemical and invasive changes that accompany its altered expression. Assay of protein and phosphorylation changes showed a downregulation of E-cadherin, upregulation of Osteopontin and a corresponding increase in phosphorylation of Focal Adhesion Kinase on Tyr397 and Tyr576 concomitant with Osteonectin induction. Melanoma cells overexpressing Osteonectin displayed increased invasive potential, whereas ablation of Osteonectin gene transcription using siRNA suppressed the invasive potential of these cells and resulted in the upregulation of E-cadherin. The recently described interaction of Osteonectin with Integrin Linked Kinase leading to modulation of its activity suggests a mechanism relevant to the loss of E-cadherin and cell adhesion that occurs during melanoma progression. These results indicate a central role for Osteonectin in the regulation of gene expression changes driving the progression of melanoma toward metastasis. © 2007 Wiley-Liss, Inc.