Open Access

Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway

  • Authors:
    • Dong Zhang
    • Songgang Wang
    • Jie Chen
    • Haitao Liu
    • Jinfa Lu
    • Hua Jiang
    • Aimin Huang
    • Yunzhen Chen
  • View Affiliations

  • Published online on: March 21, 2017     https://doi.org/10.3892/ijo.2017.3921
  • Pages: 1513-1530
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study explored the role of fibulin-4 in osteosarcoma progression and the possible signaling pathway involved. Fibulin-4 mRNA and protein expression in normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines, the normal osteoblastic cell line hFOB, and different invasive subclones were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real-time reverse transcriptase-polymerase chain reaction (real-time qRT-PCR). Using in vitro functional assays, we analyzed the invasive and proliferative abilities of different osteosarcoma cell lines and subclones with differing invasive potential. To assess the role of fibulin-4 in the invasion and metastasis of osteosarcoma cells, lentiviral vectors with fibulin-4 small hairpin RNA (shRNA) and pLVX-fibulin-4 were constructed and used to infect the highly invasive and low invasive subclones and osteosarcoma cell lines. The effects of fibulin-4 knockdown and upregulation on the biological behavior of osteosarcoma cells were investigated by functional in vitro and in vivo assays. The results revealed that fibulin-4 expression was upregulated in osteosarcoma, and was positively correlated with low differentiation, lymph node metastasis, and poor prognosis. Fibulin-4 was also found to be over-expressed in highly invasive cell lines and in the highly invasive subclones. Fibulin-4 could promote osteosarcoma cell invasion and metastasis by inducing EMT via the PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that fibulin-4 is a promoter of osteosarcoma development and progression, and suggest a novel therapeutic target for future studies.
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May-2017
Volume 50 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhang D, Wang S, Chen J, Liu H, Lu J, Jiang H, Huang A and Chen Y: Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway. Int J Oncol 50: 1513-1530, 2017
APA
Zhang, D., Wang, S., Chen, J., Liu, H., Lu, J., Jiang, H. ... Chen, Y. (2017). Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway. International Journal of Oncology, 50, 1513-1530. https://doi.org/10.3892/ijo.2017.3921
MLA
Zhang, D., Wang, S., Chen, J., Liu, H., Lu, J., Jiang, H., Huang, A., Chen, Y."Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway". International Journal of Oncology 50.5 (2017): 1513-1530.
Chicago
Zhang, D., Wang, S., Chen, J., Liu, H., Lu, J., Jiang, H., Huang, A., Chen, Y."Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K/Akt/mTOR pathway". International Journal of Oncology 50, no. 5 (2017): 1513-1530. https://doi.org/10.3892/ijo.2017.3921