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A fibrillar form of fibronectin induces apoptosis by activating SHP-2 and stress fiber formation

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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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Acknowledgements

The authors wish to thank the following members of Academia Sinica, Taiwan for their assistance: Dr. Chia-Seng Chang and Wei-Chiao Lai of the Institute of Physics for assistance in scanning electron microscopy analyses; Shu-Chen Shen of the Scientific Instrument Center for assistance in confocal microscopy analyses; and Tai-Lang Lin and the Core Facility of the Institute of Cellular and Organismic Biology for assistance in transmission electron microscopy analyses. The authors wish to thank Miranda Loney for editing the manuscript. This work was supported by grant NSC 96-2313-B-001-002 to SML from the National Science Council, Taiwan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan

    Chun-Yung Huang & Shu-Mei Liang

  2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

    Chi-Ming Liang & Jei-Ming Peng

  3. Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan

    Chi-Ming Liang

  4. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115, Taiwan

    Chun-Yung Huang, Chiao-Li Chu & Shu-Mei Liang

  5. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan

    Jei-Ming Peng

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  1. Chun-Yung Huang
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Correspondence to Chi-Ming Liang or Shu-Mei Liang.

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10495_2010_500_MOESM1_ESM.tif

Supplementary Fig. S1: The effect of G-FN on the proliferative activity of BHK-21 cells. BHK-21 cells were treated with various concentrations of G-FN, and cell proliferative activity was measured by MTT. Values represent means ± SD from two separate experiments. (TIFF 7569 kb)

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Huang, CY., Liang, CM., Chu, CL. et al. A fibrillar form of fibronectin induces apoptosis by activating SHP-2 and stress fiber formation. Apoptosis 15, 915–926 (2010). https://doi.org/10.1007/s10495-010-0500-1

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