Research Article: Involvement of c-Fos in cell proliferation, migration, and invasion in osteosarcoma cells accompanied by altered expression of Wnt2 and Fzd9

Date Published: June 30, 2017

Publisher: Public Library of Science

Author(s): Qiaozhen Wang, Huancai Liu, Qing Wang, Fenghua Zhou, Yongxin Liu, Yawen Zhang, Haoyu Ding, Meng Yuan, Fengjie Li, Yanchun Chen, Aamir Ahmad.


Osteosarcoma (OS) is an aggressive bone tumor, and proto-oncogene c-Fos is involved in this lethal disease. However, the role and molecular mechanism of c-Fos in the development and progression of OS remain enigmatic. As one of the Wnt family members, Wnt2 is closely associated with the development of several malignant tumors. In the present study, the expression of c-Fos, Wnt2, and its receptor Fzd9 in human OS tissues, MG63 OS cell line, and human osteoblast hFOB 1.19 cell line was detected by Western blot analysis, immunohistochemical staining, or reverse transcription-polymerase chain reaction. The role of c-Fos in the OS was clarified by treating MG63 cells with small interfering RNA to knockdown c-Fos. Then, cell migration and invasion were assayed by transwell assays and wound healing assay; cell proliferation was assayed by MTS method and 5-ethynyl-2′-deoxyuridine DNA proliferation in vitro detection; cell apoptosis was assayed by flow cytometric method. Co-immunoprecipitation kit was used to confirm the relationship between c-Fos and Wnt2/Fzd9. We found that the expression of c-Fos, Wnt2, and Fzd9 protein was distinctly higher in human OS tissues than that in the adjacent non-cancerous tissues, and their expression in the MG63 OS cell line was markedly increased compared with that in the human osteoblast hFOB 1.19 cell line. Knockdown of c-Fos inhibited the proliferation, migration, and invasion of MG63 cells, and promoted the apoptosis of MG63 cells. Moreover, knockdown of c-Fos inhibited the expression of Wnt2 and Fzd9 mRNA and protein. Our data enforced the evidence that knockdown of c-Fos inhibited cell proliferation, migration, and invasion, and promoted the apoptosis of OS cells accompanied by altered expression of Wnt2 and Fzd9. These findings offer new clues for OS development and progression, and c-Fos may be a potential therapeutic target for OS.

Partial Text

Osteosarcoma (OS) is characterized by formation of cancerous bone tissue, early lung-targeted metastasis, and poor prognosis; OS is also an aggressive malignant tumor of the bone occurring in children and adolescents[1, 2]. The treatment of OS is largely dependent on surgery and chemotherapy; however, the therapeutic efficacy varies among patients because OS is prone to aggressive biological behavior and development of distant metastasis[3, 4]. In recent years, although considerable research on the mechanism of OS development and metastasis has been conducted, the molecular mechanisms are still unclear.

The prognosis of OS is poor because of the early lung-targeted metastasis. As an oncogene, c-Fos is associated with the proliferation, apoptosis, migration, and invasion of tumor cells in various human cancers, including hepatocellular carcinoma, breast cancer, and prostate cancer[16, 17]. c-Fos play an oncogenic role through cooperating with c-jun in OS, and overexpression of c-Fos increased the risk of chromatin reorganization in human OS cells[18]. However, the role of c-Fos in the development and progression of OS remains unclear.




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