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Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells.
- Source :
-
Surgery [Surgery] 2004 May; Vol. 135 (5), pp. 555-62. - Publication Year :
- 2004
-
Abstract
- Background: Inadequate or inappropriate cell-substrate contact triggers a subset of apoptotic cell death, termed anoikis. Resistance to anoikis is a characteristic of malignant cells that is associated with increased tumorigenesis and metastasis. Focal adhesion kinase (FAK) is an important regulator of cell survival and migration and cell cycle progression. We tested the hypothesis that FAK gene silencing would promote anoikis and reverse acquired anoikis resistance in human pancreatic adenocarcinoma cells.<br />Methods: FAK expression was assessed by Northern and Western blot analysis. Anoikis was induced in PANC1, BxPC3, MiaPaCa2, and Mia(AR) (an anoikis-resistant derivative of MiaPaCa2) with the use of polyHEMA culture. FAK expression was suppressed by RNA interference. Anoikis was detected by YO-PRO-1/propidium iodide staining and flow cytometry. Fluorometric caspase profiling was performed. Metastasis was assayed in a nude mouse orthotopic xenograft model.<br />Results: The cell lines that were tested showed marked variation in their anoikis resistance, greater resistance being associated with higher levels of FAK expression. FAK gene silencing promoted anoikis in all cell lines and reversed acquired anoikis resistance in Mia(AR), which was associated with increased caspase activation. Suppression of FAK expression also inhibited metastasis in the nude mouse model.<br />Conclusion: FAK gene silencing suppresses anoikis resistance in pancreatic adenocarcinoma cells. FAK represents a potential target for novel antimetastatic therapies.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
Animals
Caspases metabolism
Cell Line
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
Mice
Mice, Nude
Pancreatic Neoplasms metabolism
Protein-Tyrosine Kinases metabolism
Adenocarcinoma physiopathology
Adenocarcinoma secondary
Anoikis
Gene Silencing
Pancreatic Neoplasms pathology
Pancreatic Neoplasms physiopathology
Protein-Tyrosine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0039-6060
- Volume :
- 135
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 15118593
- Full Text :
- https://doi.org/10.1016/j.surg.2003.10.017