Document Details

Document Type : Article In Journal 
Document Title :
Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade
Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade
 
Document Language : English 
Abstract : Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin's influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. 
ISSN : 1932-6203 
Journal Name : PloS one 
Volume : 7 
Issue Number : 8 
Publishing Year : 1433 AH
2012 AD 
Article Type : Article 
Added Date : Tuesday, March 8, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Jingli ZhuoZhuo, Jingli Investigator  
Ee Hong TanTan, Ee Hong Researcher  
Benedict YanYan, Benedict Researcher  
Lalchhandami TochhawngTochhawng, Lalchhandami Researcher  
Manikandan JayapalJayapal, Manikandan Researcher  
Shiuan KohKoh, Shiuan Researcher  
Hwee Kee TayTay, Hwee Kee Researcher  
Sutherland K MaciverMaciver, Sutherland K Researcher  
Shing Chuan HooiHooi, Shing Chuan Researcher  
Manuel Salto-TellezSalto-Tellez, Manuel Researcher  

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