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Nerve growth factor orchestrates NGAL and matrix metalloproteinases activity to promote colorectal cancer metastasis

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Abstract

Purpose

Colorectal cancer (CRC) is one most cancer type of high incidence and high mortality rate. Metastasis play an important role in survival rate and life quality of colorectal cancer patients. Nerve growth factor (NGF) has been shown to be involved in the metastasis and deterioration in many cancers, but the detail mechanisms in promoting the metastasis of colorectal cancer remain unknown. In this study, we aimed to explore the mechanism of NGF promoting colorectal cancer metastasis to provide new insights for developing NGF anti-colorectal cancer drugs.

Methods

We examined the expression of NGF in human colorectal cancer by immunohistochemical staining, and Western blot to evaluate the relationship between NGF and colorectal cancer metastasis. Using biochemical experiments including wound healing assay, transwell migration and invasion assay, RT–PCR, Western blot and ELISA to explore the relative mechanism of NGF promoting colorectal cancer cells metastasis in vivo.

Results

Our results found that the high expression of NGF was related with high incidence of metastasis. The binding of NGF to TrkA phosphorylated TrkA, which activated MAPK/Erk signaling pathway increasing the expression NGAL to enhance the activity of MMP2 and MMP9, promoted colorectal cancer metastasis.

Conclusion

Our finding demonstrated that NGF increased NGAL expression to enhance MMPs activity to promoted colorectal cancer cell metastasis by TrkA-MAPK/Erk axis.

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Funding

This research was funded by National Natural Science Foundation of China, grant number “81773143”; Science & Technology Department of Sichuan Province, grant number “19YYJC1252”; Health and Family Planning Commission of Sichuan Province, grant number “16PJ106/18PJ489”; The Scientific Research Fund of Chengdu Medical College, grant number “FYZX17004”.

Author information

Author notes

  1. Y. Lei, X. He, and H. Huang have contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Science, Chengdu Medical College, Chengdu, China

    Y. Lei

  2. School of Bioscience and Technology, Chengdu Medical College, Chengdu, China

    J. Lan, J. Yang & T. Zhang

  3. The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China

    X. He, W. Liu & T. Zhang

  4. Department of Gynecology and Obstetrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, China

    H. Huang

  5. School of Pharmacy, Chengdu Medical College, Chengdu, China

    Y. He

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  1. Y. Lei
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Contributions

TZ and WL conceived the experiments; YL performed the experiments and drafted the manuscript; XH and HH collected sample organization analyzed the data; YH, JL and JY performed the manuscript editing and manuscript reviewing. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to W. Liu or T. Zhang.

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Conflicts of interest

Not applicable.

Ethics approval

The study involving human samples has been approved by the Ethical Committee of Chengdu Medical College (Sichuan, China) in accordance with the Helsinki Declaration. All animal experimental were approved by the Animal Ethical Committee of Chengdu Medical College (Sichuan, China).

Informed consent

Human samples and animal experimental have been approved by the Ethical Committee of Chengdu Medical College (Sichuan, China).

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Cite this article

Lei, Y., He, X., Huang, H. et al. Nerve growth factor orchestrates NGAL and matrix metalloproteinases activity to promote colorectal cancer metastasis. Clin Transl Oncol 24, 34–47 (2022). https://doi.org/10.1007/s12094-021-02666-x

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  • DOI: https://doi.org/10.1007/s12094-021-02666-x

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