Article ; Online: Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype.
International journal of cancer
2007 Volume 121, Issue 12, Page(s) 2653–2660
Abstract: 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 ... ...
Abstract | 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 Tyr(397) and Tyr(576) 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. |
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MeSH term(s) | Cadherins/metabolism ; Cell Line, Tumor ; Cells, Cultured ; Down-Regulation ; Enzyme Induction ; Focal Adhesion Protein-Tyrosine Kinases/biosynthesis ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Melanocytes/metabolism ; Melanoma/metabolism ; Melanoma/pathology ; Neoplasm Invasiveness ; Osteonectin/genetics ; Osteonectin/metabolism ; Osteopontin/metabolism ; Phenotype ; RNA, Small Interfering/metabolism ; Transcription, Genetic ; Up-Regulation |
Chemical Substances | Cadherins ; Osteonectin ; RNA, Small Interfering ; Osteopontin (106441-73-0) ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) |
Language | English |
Publishing date | 2007-12-15 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 218257-9 |
ISSN | 1097-0215 ; 0020-7136 |
ISSN (online) | 1097-0215 |
ISSN | 0020-7136 |
DOI | 10.1002/ijc.23039 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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