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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | osteosarcoma | Research

MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

Authors: Mengkai Yang, Tao Zhang, Yangfeng Zhang, Xiaojun Ma, Jing Han, Ke Zeng, Yafei Jiang, Zongyi Wang, Zhuoying Wang, Jing Xu, Yingqi Hua, Zhengdong Cai, Wei Sun

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Background

Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown.

Methods

We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS.

Results

Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo.

Conclusion

Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients.
Appendix
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Metadata
Title
MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma
Authors
Mengkai Yang
Tao Zhang
Yangfeng Zhang
Xiaojun Ma
Jing Han
Ke Zeng
Yafei Jiang
Zongyi Wang
Zhuoying Wang
Jing Xu
Yingqi Hua
Zhengdong Cai
Wei Sun
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-01965-z

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