The small GTPase Rap1 promotes cell movement rather than stabilizes adhesion in epithelial cells responding to insulin-like growth factor I

2014 ◽  
Vol 463 (2) ◽  
pp. 257-270 ◽  
Author(s):  
Marina A. Guvakova ◽  
William S. Y. Lee ◽  
Dana K. Furstenau ◽  
Indira Prabakaran ◽  
David C. Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Cell Movement ◽  
Supporting Cell ◽  
Small Gtpase ◽  
Insulin Like Growth Factor ◽  
New Paradigm ◽  
Factor I

The present study provides evidence to support a new paradigm for understanding how the labile function of the small GTPase Rap1 is switched from supporting cell adhesion to promoting cell migration.

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 Mystique Is a New Insulin-like Growth Factor-I-regulated PDZ-LIM Domain Protein That Promotes Cell Attachment and Migration and Suppresses Anchorage-independent Growth

2005 ◽  
Vol 16 (4) ◽  
pp. 1811-1822 ◽  
Author(s):  
Gary Loughran ◽  
Nollaig C. Healy ◽  
Patrick A. Kiely ◽  
Merei Huigsloot ◽  
Nancy L. Kedersha ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Colony Formation ◽  
Insulin Like Growth Factor ◽  
Lim Domain ◽  
Lim Domain Protein ◽  
Domain Protein ◽  
And Migration ◽  
Mcf 7

By comparing differential gene expression in the insulin-like growth factor (IGF)-IR null cell fibroblast cell line (R– cells) with cells overexpressing the IGF-IR (R+ cells), we identified the Mystique gene expressed as alternatively spliced variants. The human homologue of Mystique is located on chromosome 8p21.2 and encodes a PDZ LIM domain protein (PDLIM2). GFP-Mystique was colocalized at cytoskeleton focal contacts with α-actinin and β1-integrin. Only one isoform of endogenous human Mystique protein, Mystique 2, was detected in cell lines. Mystique 2 was more abundant in nontransformed MCF10A breast epithelial cells than in MCF-7 breast carcinoma cells and was induced by IGF-I and cell adhesion. Overexpression of Mystique 2 in MCF-7 cells suppressed colony formation in soft agarose and enhanced cell adhesion to collagen and fibronectin. Point mutation of either the PDZ or LIM domain was sufficient to reverse suppression of colony formation, but mutation of the PDZ domain alone was sufficient to abolish enhanced adhesion. Knockdown of Mystique 2 with small interfering RNA abrogated both adhesion and migration in MCF10A and MCF-7 cells. The data indicate that Mystique is an IGF-IR–regulated adapter protein located at the actin cytoskeleton that is necessary for the migratory capacity of epithelial cells.

Transdifferentiation of NRP-152 rat prostatic basal epithelial cells toward a luminal phenotype: regulation by glucocorticoid, insulin-like growth factor-I and transforming growth factor-beta

1999 ◽  
Vol 112 (2) ◽  
pp. 169-179 ◽  
Author(s):  
D. Danielpour
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Tight Junction ◽  
Cell Line ◽  
Transforming Growth Factor ◽  
Insulin Like Growth Factor ◽  
Tgf Beta ◽  
Factor I ◽  
Growth Factor I ◽  
Basal Epithelial Cells

The role of basal epithelial cells in prostatic function, development and carcinogenesis is unknown. The ability of basal prostatic epithelial cells to acquire a luminal phenotype was explored in vitro using the NRP-152 rat dorsal-lateral prostate epithelial cell line as a model system. NRP-152, which was spontaneously immortalized and clonally derived, is an androgen-responsive and nontumorigenic cell line that has a basal cell phenotype under normal growth conditions. However, when placed in mitogen-deficient media, these cells undergo a dramatic morphological change to a luminal phenotype. Under these growth-restrictive conditions, immunocytochemical analysis shows that NRP-152 cells acquire the luminal markers Z0-1 (a tight-junction associated protein), occludin (integral tight-junction protein), and cytokeratin 18, and lose the basal markers cytokeratins 5 and 14. Total protein and mRNA levels of cytokeratins 8, 18, c-CAM 105 (the calcium-independent cell adhesion molecule) and Z0-1, as detected by western and/or northern blot analyses, respectively, are induced, while cytokeratin 5 and 15 are lost, and occludin is unchanged. Concomitant with this differentiation, expression of transforming growth factor-beta2 (TGF-beta2), TGF-beta3, and TGF-beta receptor type II (TbetaRII) is induced, while those of TGF-beta1 and TbetaRI remain essentially unchanged. Mitogens, such as insulin-like growth factor-I and dexamethasone inhibit luminal differentiation, while exogenous TGF-beta induces such differentiation. These data together with TGF-beta neutralization experiments using pan-specific antibody implicate an important role for autocrine TGF-beta in the induction of the luminal differentiation.

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