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Discoidin domain receptor 1 promotes lung adenocarcinoma migration via the AKT/snail signaling axis

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Abstract

Background

Discoidin domain receptor 1 (DDR1), a member of receptor tyrosine kinase, has been implicated in tumor progression. However, the function and underlying mechanism of DDR1 in lung adenocarcinoma (LUAD) progression is unclear. Thus, we explored the molecular regulatory mechanism of DDR1 in the migration of LUAD.

Methods

Transwell assays, wound healing assays and xenograft tumor assays were performed to study the function of DDR1 in the progression of LUAD. Immunoblotting and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression levels of genes. Co-immunoprecipitation (co-IP) assays were performed to detect the interaction between DDR1 and AKT. Immunofluorescence and immunohistochemistry assays were used to determine the expression level of proteins in cells and tissues, respectively.

Results

DDR1 expression was significantly higher in LUAD tissues than in normal lung tissues, and the level of DDR1 was inversely correlated with prognosis in patients. We found that DDR1 promoted the migration and invasion of LUAD cells in vitro. Furthermore, ectopic expression of DDR1 in LUAD cells altered EMT-related markers expression. Importantly, the DDR1 protein interacted with AKT and phosphorylated AKT. The AKT inhibitor MK2206 interrupted Snail upregulation in DDR1-overexpressing LUAD cells. Finally, our study revealed that depletion of DDR1 attenuated LUAD cell migration in a tumor xenograft mouse model.

Conclusion

Our findings uncovered that a high abundance of DDR1 increased the migration and invasion capability of LUAD cells via the AKT/Snail signaling axis and indicated that DDR1 could be a potential target for treating LUAD.

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Acknowledgements

We also thank the patients for their contribution in this study.

Funding

This work was supported by National Natural Science Foundation of China under (Grant No. 81902151 to L.D.); and Wenzhou Science & Technology Bureau Foundation (Grant No. Y20180074 to L.D).

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Author notes

  1. Jingjing Zhu, Huang Cheng and Lan Wang have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Jingjing Zhu, Huang Cheng, Lan Wang, Weide Xu, Qing Han, Linyong Du & Jianxin Lyu

  2. School of the 1St Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Junqing Wang

  3. Department of Health Sciences, The Graduate School of Dong-A University, Busan, Republic of Korea

    Jong-ho Lee

Authors
  1. Jingjing Zhu
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  2. Huang Cheng
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  3. Lan Wang
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  4. Weide Xu
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Contributions

JL and LD conceived the study and designed the experiments; JZ, HC, LW, and WX performed the experiments and the statistical analyses; JW and QH collected the LUAD specimens; LD and JZ drafted the manuscript; and JL proofread the paper. All authors read and approved the paper.

Corresponding authors

Correspondence to Linyong Du or Jianxin Lyu.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

All procedures performed in this study involving animal experiments approved by the Laboratory Animal Ethics Committee of Wenzhou Medical University.

Consent to participate

All the patients provided written informed consent to allow the use of their tissues in research and the use of human lung cancer specimens was approved by the Ethics Committee in first affiliated hospital of Wenzhou Medical University.

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Zhu, J., Cheng, H., Wang, L. et al. Discoidin domain receptor 1 promotes lung adenocarcinoma migration via the AKT/snail signaling axis. Mol Biol Rep 49, 7275–7286 (2022). https://doi.org/10.1007/s11033-022-07509-8

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  • DOI: https://doi.org/10.1007/s11033-022-07509-8

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