Signaling components involved in Bcl-w-induced migration of gastric cancer cells.
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.
Bae
In Hwa
IH
Laboratory of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul, South Korea.
Yoon
Sung Hwan
SH
Lee
Seung Bum
SB
Park
Jong Kuk
JK
Ho
Jin-Nyoung
JN
Um
Hong-Duck
HD
D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D016329:Sp1 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2