scholarly journals Spred2 inhibits TGF-β1-induced urokinase type plasminogen activator expression, cell motility and epithelial mesenchymal transition

2009 ◽  
Vol 127 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Victor Villar ◽  
Jelena Kocić ◽  
Juan F. Santibanez
Keyword(s):  
Cell Motility ◽  
Plasminogen Activator ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Tgf Β1

scholarly journals Estramustine Phosphate Inhibits TGF-β-Induced Mouse Macrophage Migration and Urokinase-Type Plasminogen Activator Production

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Sonja S. Mojsilovic ◽  
Slavko Mojsilovic ◽  
Suncica Bjelica ◽  
Juan F. Santibanez
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Plasminogen Activator ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Raw 264.7 ◽  
Estramustine Phosphate ◽  
Macrophage Cell ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Transforming growth factor-beta (TGF-β) has been demonstrated as a key regulator of immune responses including monocyte/macrophage functions. TGF-β regulates macrophage cell migration and polarization, as well as it is shown to modulate macrophage urokinase-type plasminogen activator (uPA) production, which also contributes to macrophage chemotaxis and migration toward damaged or inflamed tissues. Microtubule (MT) cytoskeleton dynamic plays a key role during the cell motility, and any interference on the MT network profoundly affects cell migration. In this study, by using estramustine phosphate (EP), which modifies MT stability, we analysed whether tubulin cytoskeleton contributes to TGF-β-induced macrophage cell migration and uPA expression. We found out that, in the murine macrophage cell line RAW 264.7, EP at noncytotoxic concentrations inhibited cell migration and uPA expression induced by TGF-β. Moreover, EP greatly reduced the capacity of TGF-β to trigger the phosphorylation and activation of its downstream Smad3 effector. Furthermore, Smad3 activation seems to be critical for the increased cell motility. Thus, our data suggest that EP, by interfering with MT dynamics, inhibits TGF-β-induced RAW 264.7 cell migration paralleled with reduction of uPA induction, in part by disabling Smad3 activation by TGF-β.

scholarly journals Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

2009 ◽  
Vol 20 (13) ◽  
pp. 3115-3124 ◽  
Author(s):  
Masaki Mori ◽  
Hironori Nakagami ◽  
Nobutaka Koibuchi ◽  
Koichi Miura ◽  
Yoichi Takami ◽  
...  
Keyword(s):  
Cell Motility ◽  
Heart Development ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Focal Adhesions ◽  
Atrioventricular Canal ◽  
Actin Reorganization ◽  
Mesenchymal Transition ◽  
Actin Fiber ◽  
Tgf Β1

Epithelial–mesenchymal transition (EMT) confers destabilization of cell–cell adhesion and cell motility required for morphogenesis or cancer metastasis. Here we report that zyxin, a focal adhesion-associated LIM protein, is essential for actin reorganization for cell migration in TGF-β1–induced EMT in normal murine mammary gland (NMuMG) cells. TGF-β1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-β1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-β1–dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-β1-Twist1-zyxin signal for EMT. Both zyxin and Twist1 were predominantly expressed in the cardiac atrioventricular canal (AVC) that undergoes EMT during heart development. We further performed ex vivo AVC explant assay and revealed that zyxin was required for the reorganization of actin fibers and migration of the endocardial cells. Thus, zyxin reorganizes actin fibers and enhances cell motility in response to TGF-β1, thereby regulating EMT.

scholarly journals TGFβ1-induced cell motility is mediated through Cten in colorectal cancer

2018 ◽  
Author(s):  
Abdulaziz Asiri ◽  
Teresa Pereira Raposo ◽  
Abdulaziz Alfahed ◽  
Mohammad Ilyas
Keyword(s):  
Colorectal Cancer ◽  
Cell Motility ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Growth Factor Beta ◽  
Emt Markers ◽  
Tgf Β1

ABSTRACTCten is a tensin which promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although Cten could be regulated by several cytokines and growth factors. Since Transforming growth factor beta 1 (TGF-β1) regulates integrin function and promotes EMT / cell motility, we investigated whether this happens through Cten signalling in colorectal cancer (CRC).TGF-β1 signalling was modulated by either stimulation or knockdown in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and cellular function was tested. Cten role as a direct mediator of TGF-β1 signalling was investigated in a CRC cell line with a deleted Cten gene (SW620ΔCten).When TGF-β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers. Cell migration and invasion were significantly increased following TGF-β1 stimulation and lost by TGF-β1 knockdown. TGF-β1 stimulation in SW620ΔCten resulted in selective loss of the effect of TGF-β1 signalling on EMT and cell motility whilst the stimulatory effect on cell proliferation was retained.These data suggested Cten may play an essential role in mediating TGF-β1-induced EMT and cell motility and may play a role in metastasis in CRC.

scholarly journals Rac Mediates Cytoskeletal Rearrangements and Increased Cell Motility Induced by Urokinase-Type Plasminogen Activator Receptor Binding to Vitronectin

2001 ◽  
Vol 152 (6) ◽  
pp. 1145-1158 ◽  
Author(s):  
Lars Kjøller ◽  
Alan Hall
Keyword(s):  
Cell Motility ◽  
Plasminogen Activator ◽  
Malignant Tumors ◽  
Leading Edge ◽  
Dominant Negative ◽  
Actin Reorganization ◽  
Type Plasminogen Activator ◽  
Upar Expression ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

The urokinase-type plasminogen activator receptor (uPAR) is involved in the regulation of cell motility in a variety of cell types. We show here that expression of human uPAR in growing murine fibroblasts leads to a dramatic reorganization of the actin cytoskeleton. uPAR expression induces multiple rapidly advancing protrusions that resemble the leading edge of migrating cells. The cytoskeletal changes are independent of uPA and activation of the RGD-binding activity of integrins but require uPAR binding to vitronectin (VN). The actin reorganization is blocked by coexpression of dominant negative versions of either Rac (N17Rac) or p130Cas, but not by inhibitors of Cdc42 or Rho, and is accompanied by a Rac-dependent increase in cell motility. In addition, a fourfold increase in the level of activated Rac is induced by uPAR expression. We conclude that uPAR interacts with VN both to initiate a p130Cas/Rac-dependent signaling pathway leading to actin reorganization and increased cell motility and to act as an adhesion receptor required for these responses. This mechanism may play a role in uPAR-mediated regulation of cell motility at sites where VN and uPAR are co-expressed, such as malignant tumors.

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