Document Detail

Up-regulation of fibronectin and tissue transglutaminase promotes cell invasion involving increased association with integrin and MMP expression in A431 cells.
MedLine Citation:
PMID:  21036738     Owner:  NLM     Status:  MEDLINE    
In human tumors, fibronectin (FN) expression is positively associated with tumor metastatic potential and matrix metalloproteinase (MMP) secretion. Additionally, tissue transglutaminase (TG2) is implicated as playing an important role in tumor progression, and acts as a co-receptor for integrin-mediated cell binding to FN. This study explored the involvement of FN and TG2 in cancer cell metastasis using the recently established highly invasive A431-III subline. A431-III cells expressed significantly higher levels of FN and TG2 as compared to the parental line (A431-P). Knockdown of endogenous FN by small interfering RNA (siRNA) resulted in dramatic suppression of the migratory and invasive activity, and the secreted MMP-9 activity (but not MMP-2) in A431-III subline. Exogenous administration of FN to A431-III cells also increased the secreted activity of MMP-9 but not MMP-2. Interestingly, knockdown of TG2 by siRNA dramatically reduced the cell attachment, migration and invasion, and the secretion of MMP-9 and MMP-1 (but not MMP-2 and MMP-3) in A431-III cells as compared to A431-P cells. Furthermore, A431-III cells exhibited increased association of integrin β1 and β3 with FN and TG2, and knockdown of TG2 markedly suppressed integrin β1 interaction with FN. Together, this study suggests that FN and TG2 facilitate the metastatic activity of A431 tumor cells, and this may be partly attributed to TG2 enhancement of the association of FN and β integrin. In addition, the combined targeting of TG2 and FN may be an effective therapeutic strategy for cancer displaying increased expression of both proteins.
Shih-Hsun Chen; Chun-Yu Lin; Lung-Ta Lee; Geen-Dong Chang; Ping-Ping Lee; Chin-Chun Hung; Wen-Te Kao; Pei-Hsun Tsai; Andrew V Schally; Jiuan-Jiuan Hwang; Ming-Ting Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-12-10     Revised Date:  2011-01-21    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4177-86     Citation Subset:  IM    
Institute of Biochemical Sciences, School of Life Sciences, National Taiwan University, Taipei, Taiwan, ROC.
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MeSH Terms
Antigens, CD29 / biosynthesis*,  metabolism
Cell Line, Tumor
Fibronectins / biosynthesis*,  genetics,  metabolism
Gene Knockdown Techniques
Matrix Metalloproteinase 1 / biosynthesis*
Matrix Metalloproteinase 9 / biosynthesis*
Neoplasm Invasiveness
Neoplasm Metastasis
RNA, Small Interfering / administration & dosage,  genetics
Transglutaminases / biosynthesis*,  genetics,  metabolism
Reg. No./Substance:
0/Antigens, CD29; 0/Fibronectins; 0/RNA, Small Interfering; EC; EC transglutaminase 2, human; EC Metalloproteinase 9; EC Metalloproteinase 1

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