ATF4 regulated by MYC has an important function in anoikis resistance in human osteosarcoma cells

Mo,Hao; Guan,Jian; Mo,Ligen; He,Juliang; Wu,Zhenjie; Lin,Xiang; Liu,Bin; Yuan,Zhenchao

doi:10.3892/mmr.2017.8296

ATF4 regulated by MYC has an important function in anoikis resistance in human osteosarcoma cells

Authors:
- Hao Mo
- Jian Guan
- Ligen Mo
- Juliang He
- Zhenjie Wu
- Xiang Lin
- Bin Liu
- Zhenchao Yuan
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Affiliations: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: December 18, 2017 https://doi.org/10.3892/mmr.2017.8296
Pages: 3658-3666
Copyright: © Mo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anoikis resistance is a crucial step in the process of tumor metastasis. This step determines whether the tumor cells will survive when they become detached from the extracellular matrix. However, the specific mechanism of tumor cells to bypass anoikis and become resistant remains to be elucidated. The present study aimed to determine the internal mechanism of bypassing anoikis through comparison of human osteosarcoma cell lines with human normal cell lines. High activating transcription factor 4 (ATF4) and myelocytomatosis oncogene (MYC) expression levels were observed in MG‑63 and U‑2 OS human osteosarcoma cell lines. It is possible that ATF4 and MYC contribute to tumor progression. Subsequently, the expression levels of ATF4 and MYC in HUVEC and CHON‑001 human normal cell lines were upregulated and their adhesion abilities were reduced; whereas their ability to bypass anoikis increased significantly. Simultaneously, after we Following a knock‑down ofATF4 and MYC expression levels in MG‑63 and U‑2 OS human osteosarcoma cell lines, their adhesion ability increased and their ability to bypassing anoikis was significantly reduced. Upregulation of MYC resulted in an upregulation of ATF4, and chromatin immunoprecipitation and luciferase reporter gene technology demonstrated that MYC binds to the promoter of ATF4. These findings suggest that ATF4 regulated by MYC might contribute to resistance to anoikis in human osteosarcoma cells.

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