A fibrillar form of fibronectin induces apoptosis by activating SHP-2 and stress fiber formation
Resource
APOPTOSIS, 15(8), 915-926
Journal
APOPTOSIS
Pages
915-926
Date Issued
2010
Date
2010
Author(s)
Huang, Chun-Yung
Liang, Chi-Ming
Chu, Chiao-Li
Peng, Jei-Ming
Liang, Shu-Mei
Abstract
Fibronectin (FN) is an endogenous ligand of integrins, which plays a critical role in cell adhesion and growth. Here, we converted globular FN (G-FN) into a fibrillar form (F-FN) and found that, even though both G-FN and F-FN interacted with integrin a5b1, G-FN induced cellular proliferation, whereas F-FN resulted in apoptosis that was associated with deactivation of Akt/ GSK-3b and phosphorylation of SHP-2. SHP-2 inhibitor and anti-sense oligodeoxynucleotide decreased SHP-2 level and reversed the F-FN mediated apoptosis. F-FN also induced stress fiber formation associated with activation of RhoA, Rho kinase (ROCK), and filamin. Inhibition of ROCK by ROCK inhibitor or dominant negative plasmid treatment modulated F-FN mediated apoptosis. Pharmacological studies revealed that F-FN was effective in inhibiting the survival of SKOV-3 and MCF-7 cancer cells. These findings thus demonstrate that unlike G-FN, F-FN exhibits fibrillar structure to induce cell apoptosis that is associated with phosphorylation of SHP-2, activation of RhoA/ROCK and formation of stress fibers as well as deactivation of Akt/GSK-3β. ? 2010 Springer Science+Business Media, LLC.
Subjects
Apoptosis; Fibrillar; Fibronectin; Integrin; SHP-2; Stress fiber
SDGs
Other Subjects
alpha5 integrin; antisense oligodeoxynucleotide; fibronectin; filamin; protein tyrosine phosphatase SHP 2; Rho kinase; RhoA guanine nucleotide binding protein; very late activation antigen 5; fibronectin; protein tyrosine phosphatase SHP 2; Rho kinase; apoptosis; article; cancer cell culture; cell strain MCF 7; cell survival; controlled study; enzyme activation; enzyme inactivation; enzyme inhibition; human; human cell; plasmid; priority journal; protein interaction; protein phosphorylation; protein structure; stress fiber; animal; apoptosis; cell line; cell proliferation; chemistry; cytoskeleton; metabolism; physiology; stress fiber; tumor cell line; ultrastructure; Animals; Apoptosis; Cell Line; Cell Line, Tumor; Cell Proliferation; Cytoskeleton; Enzyme Activation; Fibronectins; Humans; Protein Tyrosine Phosphatase, Non-Receptor Type 11; rho-Associated Kinases; Stress Fibers; Animals; Apoptosis; Cell Line; Cell Line, Tumor; Cell Proliferation; Cytoskeleton; Enzyme Activation; Fibronectins; Humans; Protein Tyrosine Phosphatase, Non-Receptor Type 11; rho-Associated Kinases; Stress Fibers
Type
journal article
File(s)![Thumbnail Image]()
Loading...
Name
122.pdf
Size
23.19 KB
Format
Adobe PDF
Checksum
(MD5):34f2d16f4c3cb9c899452fdf11bf65b6