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COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K/AKT Pathway

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Esophageal squamous carcinoma (ESCC) is a gastrointestinal malignancy with a high mortality, but the tumorigenesis is still unclear, restricting the target therapy development of ESCC. We explored the role of COL8A1 in ESCC development.

Methods

Tissue microarrays were used to investigate the expression level of COL8A1 in ESCC tissues. The association between COL8A1 and the overall survival of ESCC patients was assessed. The effect of differential COL8A1 expression on tumor growth was investigated by the xenograft model. The regulation of COL8A1 on tumor growth, migration, and invasion was studied by using ESCC cell lines. The signal transduction pathways involved in COL8A1 were bioinformatically profiled and validated.

Results

The COL8A1 was significantly expressed in cancerous tissues and was associated with poor prognosis in patients with ESCC. In vivo, the tumor growth obviously declined after inhibition of the COL8A1 expression. The abilities of cell proliferation and invasion were both decreased when the expression of COL8A1 was knockdown in ESCC cell line. Furthermore, we found the inactivation of the PI3K/AKT pathway that was mediated by knockdown of COL8A1 in ESCC cells, which was reversed with COL8A1 overexpression, whereas the cell proliferation and invasion ability were restored.

Conclusions

This is the first report that COL8A1 promote ESCC progression, which hopefully will provide a theoretical basis for clinical targeting of ESCC.

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Data availability

The Raw data set of this study has been uploaded on Mendeley Data Repository (https://data.mendeley.com/datasets/mkxptyh32t/draft?a=a5bf87d3-99d9-4fac-b404-01eca72de9b5), “COL8A1 and ESCC-GWY”; Mendeley Data, V1, https://doi.org/10.17632/mkxptyh32t.1).

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Acknowledgment

The authors are grateful to the Natural Science Foundation of Ningbo for supporting this project. They also thank Zhejiang University, Ningbo University and Ningbo Medical Center Lihuili Hospital for providing the platform for this research.

Funding

This study was supported by the Natural Science Foundation of Ningbo (2022J263).

Author information

Author notes

  1. Jing Hu and Pengbo Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Jing Hu MS & Senxiang Yan MD

  2. Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China

    Jing Hu MS & Xue Chen MS

  3. The Affiliated Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, China

    Pengbo Li MS

  4. Department of Cardiothoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China

    Yanggang Dan MS & Zhe Chen MS

  5. Department of General Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China

    Yeting Lu MS

Authors
  1. Jing Hu MS
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  2. Pengbo Li MS
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  4. Zhe Chen MS
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Contributions

JH and PL: Equal contribution, study design, most parts of experiments, wrote the main manuscript text. YD, ZC: data collection and verification. YL, XC: data analysis and discussion. SY: Supervision, advice, and funding. All authors reviewed the manuscript.

Corresponding author

Correspondence to Senxiang Yan MD.

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Disclosure

The authors declare no conflicts of interest.

Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki. This work was strictly performed in accordance with the protocols approved by the Ningbo Medical Center Lihuili Hospital Animal Care Committee and Ethics Committee of Shanghai OUTDO BIOTECH Ltd (SHYJS-CP-1707008).

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Hu, J., Li, P., Dan, Y. et al. COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K/AKT Pathway. Ann Surg Oncol 31, 3502–3512 (2024). https://doi.org/10.1245/s10434-023-14370-x

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  • DOI: https://doi.org/10.1245/s10434-023-14370-x

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