Increased transcriptional response to mechanical strain in keloid fibroblasts due to increased focal adhesion complex formation

2005 ◽  
Vol 206 (2) ◽  
pp. 510-517 ◽  
Author(s):  
Zhen Wang ◽  
Kenton D. Fong ◽  
Toan-Thang Phan ◽  
Ivor J. Lim ◽  
Michael T. Longaker ◽  
...  
Keyword(s):  
Complex Formation ◽  
Focal Adhesion ◽  
Mechanical Strain ◽  
Transcriptional Response ◽  
Focal Adhesion Complex ◽  
Adhesion Complex ◽  
Keloid Fibroblasts

Beta3-integrin–mediated focal adhesion complex formation: adult cardiocytes embedded in three-dimensional polymer matrices

1999 ◽  
Vol 83 (12) ◽  
pp. 38-43 ◽  
Author(s):  
Toshio Nagai ◽  
Martin Laser ◽  
Catalin F Baicu ◽  
Michael R Zile ◽  
George Cooper ◽  
...  
Keyword(s):  
Complex Formation ◽  
Focal Adhesion ◽  
Three Dimensional ◽  
Polymer Matrices ◽  
Focal Adhesion Complex ◽  
Beta3 Integrin ◽  
Adhesion Complex

scholarly journals Abnormalities in focal adhesion complex formation, regulation, and function in human autosomal recessive polycystic kidney disease epithelial cells

2010 ◽  
Vol 298 (4) ◽  
pp. C831-C846 ◽  
Author(s):  
Sharon Israeli ◽  
Kurt Amsler ◽  
Nadezhda Zheleznova ◽  
Patricia D. Wilson
Keyword(s):  
Kidney Disease ◽  
Epithelial Cells ◽  
Complex Formation ◽  
Polycystic Kidney Disease ◽  
Focal Adhesion ◽  
Autosomal Recessive ◽  
Polycystic Kidney ◽  
Focal Adhesion Complex ◽  
Collecting Tubules ◽  
Adhesion Complex

Integrin-associated focal adhesion complex formation and turnover plays an essential role in directing interactions between epithelial cells and the extracellular matrix during organogenesis, leading to appropriate cell spreading, cell-matrix adhesion, and migration. Autosomal recessive polycystic kidney disease (ARPKD) is associated with loss of function of PKHD1-encoded protein fibrocystin-1 and is characterized by cystic dilation of renal collecting tubules (CT) in utero and loss of renal function in patients if they survive the perinatal period. Normal polycystin-1 (PC-1)/focal adhesion complex function is required for control of CT diameter during renal development, and abnormalities in these complexes have been demonstrated in human PC-1 mutant cystic cells. To determine whether loss of fibrocystin-1 was associated with focal adhesion abnormalities, ARPKD cells or normal age-matched human fetal (HF)CT cells in which fibrocystin-1 had been decreased by 85% by small interfering RNA inhibition were compared with normal HFCT. Accelerated attachment and spreading on collagen matrix and decreased motility of fibrocystin-1-deficient cells were associated with longer paxillin-containing focal adhesions, more complex actin-cytoskeletal rearrangements, and increased levels of total β1-integrin, c-Src, and paxillin. Immunoblot analysis of adhesive cells using site-specific phospho-antibodies demonstrated ARPKD-associated loss of activation of focal adhesion kinase (FAK) by phosphorylation at its autophosphorylation site (Y397); accelerated FAK inhibition by phosphorylation at Y407, S843, and S910; as well as increased activation of c-Src at pY418. Paxillin coimmunoprecipitation analyses suggested that fibrocystin-1 was a component of the normal focal adhesion complex and that actin and fibrocystin-1 were lost from ARPKD complexes.

scholarly journals The regulation of focal adhesion complex formation and salivary gland epithelial cell organization by nanofibrous PLGA scaffolds

Biomaterials ◽  
2012 ◽  
Vol 33 (11) ◽  
pp. 3175-3186 ◽  
Author(s):  
Sharon J. Sequeira ◽  
David A. Soscia ◽  
Basak Oztan ◽  
Aaron P. Mosier ◽  
Riffard Jean-Gilles ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Epithelial Cell ◽  
Complex Formation ◽  
Focal Adhesion ◽  
Focal Adhesion Complex ◽  
Salivary Gland Epithelial Cell ◽  
Cell Organization ◽  
Adhesion Complex

scholarly journals PHIP drives glioblastoma motility and invasion by regulating the focal adhesion complex

2020 ◽  
Vol 117 (16) ◽  
pp. 9064-9073
Author(s):  
David de Semir ◽  
Vladimir Bezrookove ◽  
Mehdi Nosrati ◽  
Kara R. Scanlon ◽  
Eric Singer ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Pleckstrin Homology Domain ◽  
Physical Interaction ◽  
Glioblastoma Cells ◽  
Focal Adhesion Complex ◽  
Adhesion Proteins ◽  
Focal Adhesion Proteins ◽  
Tumor Cell Motility ◽  
Adhesion Complex ◽  
Force Transduction

The invasive behavior of glioblastoma is essential to its aggressive potential. Here, we show that pleckstrin homology domain interacting protein (PHIP), acting through effects on the force transduction layer of the focal adhesion complex, drives glioblastoma motility and invasion. Immunofluorescence analysis localized PHIP to the leading edge of glioblastoma cells, together with several focal adhesion proteins: vinculin (VCL), talin 1 (TLN1), integrin beta 1 (ITGB1), as well as phosphorylated forms of paxillin (pPXN) and focal adhesion kinase (pFAK). Confocal microscopy specifically localized PHIP to the force transduction layer, together with TLN1 and VCL. Immunoprecipitation revealed a physical interaction between PHIP and VCL. Targeted suppression of PHIP resulted in significant down-regulation of these focal adhesion proteins, along with zyxin (ZYX), and produced profoundly disorganized stress fibers. Live-cell imaging of glioblastoma cells overexpressing a ZYX-GFP construct demonstrated a role for PHIP in regulating focal adhesion dynamics. PHIP silencing significantly suppressed the migratory and invasive capacity of glioblastoma cells, partially restored following TLN1 or ZYX cDNA overexpression. PHIP knockdown produced substantial suppression of tumor growth upon intracranial implantation, as well as significantly reduced microvessel density and secreted VEGF levels. PHIP copy number was elevated in the classical glioblastoma subtype and correlated with elevated EGFR levels. These results demonstrate PHIP’s role in regulating the actin cytoskeleton, focal adhesion dynamics, and tumor cell motility, and identify PHIP as a key driver of glioblastoma migration and invasion.

scholarly journals Altered Actin Dynamics in Cell Migration of GNE Mutant Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Shamulailatpam Shreedarshanee Devi ◽  
Rashmi Yadav ◽  
Ranjana Arya
Keyword(s):  
Signal Transduction ◽  
Cell Migration ◽  
Sialic Acid ◽  
Focal Adhesion ◽  
Actin Polymerization ◽  
Cytoskeletal Proteins ◽  
Confocal Imaging ◽  
Actin Dynamics ◽  
Focal Adhesion Complex ◽  
Adhesion Complex

Cell migration is an essential cellular process that requires coordination of cytoskeletal dynamics, reorganization, and signal transduction. The actin cytoskeleton is central in maintaining the cellular structure as well as regulating the mechanisms of cell motility. Glycosylation, particularly sialylation of cell surface proteins like integrins, regulates signal transduction from the extracellular matrix to the cytoskeletal network. The activation of integrin by extracellular cues leads to recruitment of different focal adhesion complex proteins (Src, FAK, paxillin, etc.) and activates the signal including Rho GTPases for the regulation of actin assembly and disassembly. During cell migration, the assembly and disassembly of actin filament provides the essential force for the cell to move. Abnormal sialylation can lead to actin signaling dysfunction leading to aberrant cell migration, one of the main characteristics of cancer and myopathies. In the present study, we have reported altered F-actin to G-actin ratios in GNE mutated cells. These cells exhibit pathologically relevant mutations of GNE (UDP N-acetylneuraminic 2-epimerase/N-acetylmannosamine kinase), a key sialic acid biosynthetic enzyme. It was found that GNE neither affects the actin polymerization nor binds directly to actin. However, mutation in GNE resulted in increased binding of α-actinin to actin filaments. Further, through confocal imaging, GNE was found to be localized in focal adhesion complex along with paxillin. We further elucidated that mutation in GNE resulted in upregulation of RhoA protein and Cofilin activity is downregulated, which could be rescued with Rhosin and chlorogenic acid, respectively. Lastly, mutant in GNE reduced cell migration as implicated from wound healing assay. Our study indicates that molecules altering Cofilin function could significantly revert the cell migration defect due to GNE mutation in sialic acid-deficient cells. We propose cytoskeletal proteins to be alternate drug targets for disorders associated with GNE such as GNE myopathy.

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