Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade


Autoria(s): Zhuo, Jingli; Tan, Ee Hong; Yan, Benedict; Tochhawng, Lalchhandami; Jayapal, Manikandan; Koh, Shiuan; Tay, Hwee Kee; Maciver, Sutherland K; Hooi, Shing Chuan; Salto-Tellez, Manuel; Kumar, Alan Prem; Goh, Yaw Chong; Lim, Yaw Chyn; Yap, Celestial T
Data(s)

2012

Resumo

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.

Identificador

http://pure.qub.ac.uk/portal/en/publications/gelsolin-induces-colorectal-tumor-cell-invasion-via-modulation-of-the-urokinasetype-plasminogen-activator-cascade(ccb3d675-3623-4961-918d-e4e49eaf0715).html

http://dx.doi.org/10.1371/journal.pone.0043594

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Zhuo , J , Tan , E H , Yan , B , Tochhawng , L , Jayapal , M , Koh , S , Tay , H K , Maciver , S K , Hooi , S C , Salto-Tellez , M , Kumar , A P , Goh , Y C , Lim , Y C & Yap , C T 2012 , ' Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade ' PloS one , vol 7 , no. 8 , pp. e43594 . DOI: 10.1371/journal.pone.0043594

Palavras-Chave #Gene Expression Regulation, Neoplastic #Neoplasm Invasiveness #Gene Silencing #Humans #Fibrinolysin #Gelsolin #Urokinase-Type Plasminogen Activator #Receptors, Urokinase Plasminogen Activator #Cell Line, Tumor #RNA, Small Interfering #Signal Transduction #Colorectal Neoplasms
Tipo

article