Epigenetic regulation of integrin-linked kinase expression depending on adhesion of gastric carcinoma cells

2007 ◽  
Vol 292 (2) ◽  
pp. C857-C866 ◽  
Author(s):  
Yong-Bae Kim ◽  
Sung-Yul Lee ◽  
Sang-Kyu Ye ◽  
Jung Weon Lee
Keyword(s):  
Cell Adhesion ◽  
Gastric Carcinoma ◽  
Transforming Growth Factor ◽  
Soft Agar ◽  
Transforming Growth Factor Β1 ◽  
Carcinoma Cells ◽  
Adherent Cells ◽  
Gene Expressions ◽  
Integrin Linked Kinase ◽  
Suspended Cells

Cell adhesion to the extracellular matrix (ECM) regulates gene expressions in diverse dynamic environments. However, the manner in which gene expressions are regulated by extracellular cues is largely unknown. In this study, suspended gastric carcinoma cells showed higher basal and transforming growth factor-β1 (TGFβ1)-mediated acetylations of histone 3 (H3) and Lys9of H3 and levels of integrin-linked kinase (ILK) mRNA and protein than did fibronectin-adherent cells did. Moreover, the insignificant acetylation and ILK expression in adherent cells were recovered by alterations of integrin signaling and actin organization, indicating a connection between cytoplasmic and nuclear changes. Higher acetylations in suspended cells were correlated with associations between Smad4, p300/CBP, and Lys9-acetylated H3. Meanwhile, adherent cells showed more associations between HDAC3, Ski, and MeCP2. Chromatin immunoprecipitations with anti-acetylated H3, Lys9-acetylated H3, or p300/CBP antibody resulted in more coprecipitated ILK promoter, correlated with enhanced ILK mRNA and protein levels, in suspended cells. Moreover, ILK expression inversely regulated cell adhesion to ECM proteins, and its overexpression enhanced cell growth in soft agar. These observations indicate that cell adhesion and/or its related molecular basis regulate epigenetic mechanisms leading to a loss of ILK transcription, which in turn regulates cell adhesion property in a feedback linkage.

scholarly journals TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

2004 ◽  
Vol 379 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hwang-Phill KIM ◽  
Mi-Sook LEE ◽  
Jiyon YU ◽  
Jin-Ah PARK ◽  
Hyun-Soon JONG ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Gastric Carcinoma ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Carcinoma Cells ◽  
Matrix Proteins ◽  
Src Family Kinase ◽  
Extracellular Signal ◽  
Activity Dependent ◽  
Tgf Β1

Signalling by integrin-mediated cell anchorage to extracellular matrix proteins is co-operative with other receptor-mediated signalling pathways to regulate cell adhesion, spreading, proliferation, survival, migration, differentiation and gene expression. It was observed that an anchorage-independent gastric carcinoma cell line (SNU16) became adherent on TGF-β1 (transforming growth factor β1) treatment. To understand how a signal cross-talk between integrin and TGF-β1 pathways forms the basis for TGF-β1 effects, cell adhesion and signalling activities were studied using an adherent subline (SNU16Ad, an adherent variant cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad cells, but not integrin α5-expressing SNU16 cells, showed an increase in adhesion on extracellular matrix proteins after TGF-β1 treatment. This increase was shown to be mediated by an integrin α3 subunit, which was up-regulated in adherent SNU16Ad cells and in TGF-β1-treated SNU16 cells, compared with the parental SNU16 cells. After TGF-β1 treatment of SNU16Ad cells on fibronectin, Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP loading and ERK1/ERK2 (extracellular-signal-regulated kinases 1 and 2) activity were decreased, which showed a dependence on c-Src family kinase activity. Studies on adhesion and signalling activities using pharmacological inhibitors or by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity increased TGF-β1-mediated cell adhesion slightly, but not the basal cell adhesion significantly, and that c-Src family kinase activity and decrease in Ras/ERKs cascade activity were required for the TGF-β1 effects. Altogether, the present study indicates that TGF-β1 treatment causes anchorage-independent gastric carcinoma cells to adhere by an increase in integrin α3 level and a c-Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.

scholarly journals The Signaling Network of Transforming Growth Factor β1, Protein Kinase Cδ, and Integrin Underlies the Spreading and Invasiveness of Gastric Carcinoma Cells

2005 ◽  
Vol 25 (16) ◽  
pp. 6921-6936 ◽  
Author(s):  
Mi-Sook Lee ◽  
Tae Young Kim ◽  
Yong-Bae Kim ◽  
Sung-Yul Lee ◽  
Seong-Gyu Ko ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Gastric Carcinoma ◽  
Transforming Growth Factor ◽  
Carcinoma Cell ◽  
Cell Spreading ◽  
Transforming Growth Factor Β1 ◽  
Gastric Carcinoma Cell ◽  
Spreading Behavior ◽  
Protein Kinase Cδ

ABSTRACT Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor β1 (TGFβ1) pathway that is mediated by protein kinase Cδ (PKCδ). TGFβ1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKCδ, which is required for expression and activation of integrins. Increased expression of integrins α2 and α3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGFβ1 effects. Furthermore, TGFβ1 treatment and PKCδ activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGFβ pathway, PKCδ expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.

scholarly journals Rapid Up-Regulation of α4 Integrin-mediated Leukocyte Adhesion by Transforming Growth Factor-β1

2003 ◽  
Vol 14 (1) ◽  
pp. 54-66 ◽  
Author(s):  
Rubén A. Bartolomé ◽  
Francisco Sanz-Rodrı́guez ◽  
Mar M. Robledo ◽  
Andrés Hidalgo ◽  
Joaquin Teixidó
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Peripheral Blood ◽  
Transforming Growth Factor Β1 ◽  
Small Gtpase ◽  
Mitogen Activated Protein Kinase ◽  
Intracellular Camp ◽  
Tgf Β1

The α4 integrins (α4β1 and α4β7) are cell surface heterodimers expressed mostly on leukocytes that mediate cell-cell and cell-extracellular matrix adhesion. A characteristic feature of α4 integrins is that their adhesive activity can be subjected to rapid modulation during the process of cell migration. Herein, we show that transforming growth factor-β1 (TGF-β1) rapidly (0.5–5 min) and transiently up-regulated α4 integrin-dependent adhesion of different human leukocyte cell lines and human peripheral blood lymphocytes (PBLs) to their ligands vascular cell adhesion molecule-1 (VCAM-1) and connecting segment-1/fibronectin. In addition, TGF-β1 enhanced the α4 integrin-mediated adhesion of PBLs to tumor necrosis factor-α–treated human umbilical vein endothelial cells, indicating the stimulation of α4β1/VCAM-1 interaction. Although TGF-β1 rapidly activated the small GTPase RhoA and the p38 mitogen-activated protein kinase, enhanced adhesion did not require activation of both signaling molecules. Instead, polymerization of actin cytoskeleton triggered by TGF-β1 was necessary for α4 integrin-dependent up-regulated adhesion, and elevation of intracellular cAMP opposed this up-regulation. Moreover, TGF-β1 further increased cell adhesion mediated by α4 integrins in response to the chemokine stromal cell-derived factor-1α. These data suggest that TGF-β1 can potentially contribute to cell migration by dynamically regulating cell adhesion mediated by α4 integrins.

scholarly journals Mouse forestomach carcinoma cells immunosuppress macrophages through transforming growth factor-β1

2012 ◽  
Vol 5 (4) ◽  
pp. 988-992 ◽  
Author(s):  
HUAXING LUO ◽  
YINGXUE HAO ◽  
BO TANG ◽  
DONGZHU ZENG ◽  
YAN SHI ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Carcinoma Cells
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