A fibrillar form of fibronectin induces apoptosis by activating SHP-2 and stress fiber formation |
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Authors: | Chun-Yung Huang Chi-Ming Liang Chiao-Li Chu Jei-Ming Peng Shu-Mei Liang |
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Institution: | (1) Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan;(2) Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan;(3) Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan;(4) Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115, Taiwan;(5) Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan; |
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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 α5β1,
G-FN induced cellular proliferation, whereas F-FN resulted in apoptosis that was associated with deactivation of Akt/GSK-3β
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. |
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