Up-regulation of Fibronectin and Tissue Transglutaminase Promotes Cell Invasion Involving Increased Association with Integrin and MMP Expression in A431 Cells
Resource
Anticancer Research, 30(10), 4177-4186
Journal
Anticancer Research
Journal Volume
30
Journal Issue
10
Pages
4177-4186
Date Issued
2010
Date
2010
Author(s)
Chen, Shih-Hsun
Abstract
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.
Subjects
A431 cell; Fibronectin; MMP-9; TG2
SDGs
Other Subjects
beta1 integrin; beta3 integrin; fibronectin; gelatinase A; gelatinase B; integrin; interstitial collagenase; matrix metalloproteinase; protein glutamine gamma glutamyltransferase antibody; small interfering RNA; stromelysin; article; cancer invasion; cell adhesion; cell invasion; cell line; cell migration; cell strain a 431; controlled study; enzyme release; in vitro study; metastasis; priority journal; protein expression; protein protein interaction; upregulation; Antigens, CD29; Cell Line, Tumor; Fibronectins; Gene Knockdown Techniques; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Metastasis; RNA, Small Interfering; Transglutaminases; Up-Regulation
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