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ENO1 promotes immunosuppression and tumor growth in pancreatic cancer

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Abstract

Background

Pancreatic adenocarcinoma (PAAD) is a highly aggressive and malignant cancer type with the highest mortality rate of all major cancers. However, the molecular and tumor immune escape mechanism underlying pancreatic cancer remains largely unclear. α-enolase (ENO1) is a glycolytic enzyme reported to overexpress in a variety of cancer types. This study was undertaken to investigate the functional role and therapeutic potential of ENO1 in pancreatic cancer.

Methods

We examined the expression levels of ENO1 across a broad spectrum of cancer types from the TCGA database. ENO1-knockout (ENO1-KO) through CRISPR/CAS9 technology in a mouse pancreatic cancer cell line (PAN02) was used to analyze the role of ENO1 on proliferation and colony formation. Flow cytometry and RT-PCR were also applied to analyze T lymphocytes and relevant cytokines.

Results

In the present study, we identified that ENO1 promoted pancreatic cancer cell proliferation. Our bioinformatics data indicated that ENO1 was significantly overexpressed in pancreatic cancer cell lines and tissues. Survival analyses revealed that ENO1 overexpression implicated poor survival of PAAD patients. Knockout of ENO1 expression repressed the ability of proliferation and colony formation in PAN02. In addition, ENO1-KO significantly decreased tumor growth in mouse models. Further flow cytometry and RT-PCR analysis revealed that ENO1-KO modulates the tumor microenvironment (TME), especially in suppressed Treg cells and inducing anti-tumor cytokine responses.

Conclusions

Taken together, our data showed that ENO1 was an oncogenic biomarker and might serve as a promising target for immunotherapy of pancreatic cancer.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Funding

This work was funded by grants from the Shanghai Rising-Star Program (19QA1404900, Y.P.), the Science and Technology Commission of Shanghai Municipality (18ZR1419400, Y.P.) and the Shanghai Jiao Tong University Foundation (YG2022QN033).

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, University of California, Berkeley, 110 Sproul Hall, Berkeley, CA, 94720, USA

    Chen Kai Huang

  2. MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Lei Lv

  3. Department of Oncology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China

    Huanliang Chen

  4. Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, 280 South Chongqing Road, Shanghai, 200025, China

    Ying Sun

  5. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China

    Yong Ping

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  1. Chen Kai Huang
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Contributions

Conceptualization: CKH and YP; methodology: CKH, YS, and YP; investigation: CKH, HLC, and YS; writing—original draft: CKH; writing—review and editing: CKH, LL, HLC, YS, and YP; funding acquisition: YP; resources: LL, YS, and YP; supervision: LL, YS, and YP.

Corresponding authors

Correspondence to Ying Sun or Yong Ping.

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Conflict of interest

The authors declare no competing interests.

Ethics approval

All mice were maintained under pathogen-free conditions at Shanghai Jiao Tong University School of Medicine. All experimental procedures were approved by Institutional Animal Care and Use Committee (IACUC Number-A-2019-077) of Shanghai Jiao Tong University School of Medicine.

Informed consent

There were no clinical trials involving human subjects in this study, so informed consent is not applicable.

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Huang, C.K., Lv, L., Chen, H. et al. ENO1 promotes immunosuppression and tumor growth in pancreatic cancer. Clin Transl Oncol 25, 2250–2264 (2023). https://doi.org/10.1007/s12094-023-03114-8

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  • DOI: https://doi.org/10.1007/s12094-023-03114-8

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