scholarly journals Inhibition of transforming growth factor-β-activated kinase-1 blocks cancer cell adhesion, invasion, and metastasis

2012 ◽  
Vol 107 (1) ◽  
pp. 129-136 ◽  
Author(s):  
D M Ray ◽  
P H Myers ◽  
J T Painter ◽  
M J Hoenerhoff ◽  
K Olden ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Cancer Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Invasion And Metastasis ◽  
Cancer Cell Adhesion

scholarly journals BMP-1 disrupts cell adhesion and enhances TGF-β activation through cleavage of the matricellular protein thrombospondin-1

2020 ◽  
Vol 13 (639) ◽  
pp. eaba3880 ◽  
Author(s):  
Cyril Anastasi ◽  
Patricia Rousselle ◽  
Maya Talantikite ◽  
Agnès Tessier ◽  
Caroline Cluzel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Substantial Effect ◽  
Matricellular Protein ◽  
Matrix Assembly ◽  
Morphogenetic Protein ◽  
Thrombospondin 1

Bone morphogenetic protein 1 (BMP-1) is an important metalloproteinase that synchronizes growth factor activation with extracellular matrix assembly during morphogenesis and tissue repair. The mechanisms by which BMP-1 exerts these effects are highly context dependent. Because BMP-1 overexpression induces marked phenotypic changes in two human cell lines (HT1080 and 293-EBNA cells), we investigated how BMP-1 simultaneously affects cell-matrix interactions and growth factor activity in these cells. Increasing BMP-1 led to a loss of cell adhesion that depended on the matricellular glycoprotein thrombospondin-1 (TSP-1). BMP-1 cleaved TSP-1 between the VWFC/procollagen-like domain and the type 1 repeats that mediate several key TSP-1 functions. This cleavage induced the release of TSP-1 C-terminal domains from the extracellular matrix and abolished its previously described multisite cooperative interactions with heparan sulfate proteoglycans and CD36 on HT1080 cells. In addition, BMP-1–dependent proteolysis potentiated the TSP-1–mediated activation of latent transforming growth factor–β (TGF-β), leading to increased signaling through the canonical SMAD pathway. In primary human corneal stromal cells (keratocytes), endogenous BMP-1 cleaved TSP-1, and the addition of exogenous BMP-1 enhanced cleavage, but this had no substantial effect on cell adhesion. Instead, processed TSP-1 promoted the differentiation of keratocytes into myofibroblasts and stimulated production of the myofibroblast marker α-SMA, consistent with the presence of processed TSP-1 in human corneal scars. Our results indicate that BMP-1 can both trigger the disruption of cell adhesion and stimulate TGF-β signaling in TSP-1–rich microenvironments, which has important potential consequences for wound healing and tumor progression.

Decreased TumorigenicityIn VivoWhen Transforming Growth Factor β Treatment Causes Cancer Cell Senescence

2003 ◽  
Vol 67 (4) ◽  
pp. 815-821 ◽  
Author(s):  
Yoshinori KATAKURA ◽  
Eriko NAKATA ◽  
Yukiko TABIRA ◽  
Takumi MIURA ◽  
Kiichiro TERUYA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Senescence
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