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Intestinal epithelial SNAI1 promotes the occurrence of colorectal cancer by enhancing EMT and Wnt/β-catenin signaling

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Abstract

Colorectal cancer (CRC) is a prevalent cause of cancer and mortality on a global scale. SNAI1, a member of the zinc finger transcription superfamily, is a significant contributor to embryonic development and carcinogenesis through the process of epithelial–mesenchymal transition (EMT). While prior research utilizing CRC cells and clinical data has demonstrated that SNAI1 facilitates CRC progression through diverse mechanisms, the precise manner in which epithelial SNAI1 regulates CRC development in vivo remains unclear. In this study, colitis and colitis-associated CRC were induced through the use of intestinal epithelium-specific Snai1 knockout (Snai1 cKO) mice. Our findings indicate that Snai1 cKO mice exhibit a reduced susceptibility to acute colitis and colitis-associated CRC compared to control mice. Western-blot analysis of colon tissues revealed that Snai1 cKO mice exhibited a higher overall apoptosis level during tumor formation than control mice. No significant differences were observed in the activation of the classical p53 signaling pathway. However, Snai1 cKO mice exhibited weakened EMT and Wnt/β-catenin pathway activation. In summary, our study has provided evidence in vivo that the intestinal epithelial SNAI1 protein suppresses apoptosis, amplifies the EMT, and activates the Wnt/β-catenin signaling pathways in both early and late phases of CRC formation, thus promoting the development and progression of colitis-associated CRC.

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Data will be made available upon reasonable request.

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Funding

This study was funded by National Natural Science Foundation of China (31960163), The Jinggang Scholar Program of Jiangxi Province (QD202205), The Research Team Project of Gannan Medical University (TD2021JC01) (To Zhiping Liu), The Project of Department of Education of Jiangxi Province (GJJ211539) (To Yayun Chen), and Doctor Startup Fund of The First Affiliated Hospital of Gannan Medical University and Jiangxi Education Department Fund (QD097, GJJ2201437) (To Qiuxiang Xiao).

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Author notes

  1. Furong Qing, Junxia Xue, and Lina Sui are co-first authors.

Authors and Affiliations

  1. School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China

    Furong Qing, Lina Sui, Yayun Chen & Zhiping Liu

  2. Department of Clinical Laboratory, People’s Hospital of Xiangshui, Yancheng, Jiangsu, 224600, China

    Junxia Xue

  3. Department of Pathology, The First Affiliated Hospital, Ganzhou, Jiangxi, 341000, China

    Qiuxiang Xiao

  4. Center for Scientific Research, Ganzhou, Jiangxi, 341000, China

    Tao Xie & Zhiping Liu

  5. Department of Clinical Laboratory, The First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, 341000, China

    Junyun Huang

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  1. Furong Qing
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Contributions

FQ, JX, and LS performed experiments, data analysis and interpretation, and drafted the manuscript; QX, TX, and YC performed part of experiments; ZL and JH designed the study and revised the manuscript.

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Correspondence to Junyun Huang or Zhiping Liu.

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Qing, F., Xue, J., Sui, L. et al. Intestinal epithelial SNAI1 promotes the occurrence of colorectal cancer by enhancing EMT and Wnt/β-catenin signaling. Med Oncol 41, 34 (2024). https://doi.org/10.1007/s12032-023-02253-w

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  • DOI: https://doi.org/10.1007/s12032-023-02253-w

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