Signaling components involved in Bcl-w-induced migration of gastric cancer cells

• Published in: Cancer letters Vol. 277; no. 1; pp. 22 - 28
• Main Authors: Bae, In Hwa, Yoon, Sung Hwan, Lee, Seung Bum, Park, Jong Kuk, Ho, Jin-Nyoung, Um, Hong-Duck
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.05.2009; Elsevier Limited
• Subjects: Apoptosis Regulatory Proteins - physiology; Bcl-w; Cell adhesion & migration; Cell culture; Cell Line, Tumor; Cell Movement; Cell signaling; Enzymes; Focal Adhesion Protein-Tyrosine Kinases - physiology; Gastric cancer; Gastric carcinoma; Hematology, Oncology and Palliative Medicine; Humans; Kinases; Matrix Metalloproteinase 2 - physiology; Migration; Phosphatidylinositol 3-Kinases - physiology; Phosphorylation; Proteins; Proto-Oncogene Proteins c-akt - physiology; Signal Transduction - physiology; Sp1 Transcription Factor - physiology; Stomach Neoplasms - pathology; Studies; Urokinase-Type Plasminogen Activator - physiology; Gastric carcinoma; Bcl-w; Migration; Cell signaling
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2008.11.022

Abstract We have previously reported that Bcl-w enhances the invasiveness of gastric cancer cells by inducing MMP-2 expression via phosphoinositide 3-kinase (PI3K), Akt and Sp1. This study demonstrates that Bcl-w additionally induces uPA expression and FAK activation. Analyses of the hierarchical relationship and functions of these components showed that the PI3K-Akt-Sp1 pathway also mediates the induction of uPA, and that both uPA and MMP-2 contribute to Bcl-w-induced invasion via the stimulation of the FAK-dependent migratory pathway. These findings significantly advance our understandings of the Bcl-w-induced signaling processes that results in the migration and invasion of cancer cells.