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TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways

  • Authors:
    • Xiaopeng Zhao
    • Lu Ma
    • Lu Dai
    • Di Zuo
    • Xin Li
    • Hongli Zhu
    • Fang Xu
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Gynecology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712000, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 577-588
    |
    Published online on: June 4, 2020
       https://doi.org/10.3892/or.2020.7631
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Abstract

Cancer stem cells are responsible for tumorigenesis, progression, recurrence and metastasis. Intestinal stem cells (ISCs) are regarded as the origin of intestinal neoplasia. Inflammation also serves an important role in intestinal neoplasia. To explore the molecular mechanisms underlying the inflammation‑mediated induction of intestinal tumorigenesis, the present study investigated the function of tumor necrosis factor (TNF)‑α in the malignant transformation of ISCs. NCM460 spheroid (NCM460s) cells with higher expression of stem cell genes, such as Oct4, Nanog, Sox2 and Lgr5, and with a higher ratio of CD133+, were obtained from NCM460 cells in serum‑free medium. TNF‑α accelerated cell proliferation, migration and invasion, induced chemotherapy resistance and the epithelial‑mesenchymal transition. NF‑κB and Wnt/β‑catenin pathways were activated in TNF‑α‑induced inflammatory responses, leading to the nuclear translocation of p65 and β‑catenin, as well as promoter activity of NF‑κB and TCF/LEF transcription factors. It was further demonstrated that TNF‑α‑induced activation of the NF‑κB and Wnt/β‑catenin signaling pathways, as well as the upregulation of proinflammatory cytokines, were significantly suppressed by p65‑knockdown. Notably, PDTC, an inhibitor of NF‑κB signaling, reversed TNF‑α‑induced activation of the NF‑κB and Wnt/β‑catenin pathways. A similar role was observed for IWP‑2, an inhibitor of Wnt/β‑catenin signaling. Collectively, these results demonstrated that the NF‑κB and Wnt/β‑catenin pathways were activated to promote TNF‑α‑induced malignant transformation of ISCs, in which these two pathways cross‑regulated each other.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao X, Ma L, Dai L, Zuo D, Li X, Zhu H and Xu F: TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways. Oncol Rep 44: 577-588, 2020.
APA
Zhao, X., Ma, L., Dai, L., Zuo, D., Li, X., Zhu, H., & Xu, F. (2020). TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways. Oncology Reports, 44, 577-588. https://doi.org/10.3892/or.2020.7631
MLA
Zhao, X., Ma, L., Dai, L., Zuo, D., Li, X., Zhu, H., Xu, F."TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways". Oncology Reports 44.2 (2020): 577-588.
Chicago
Zhao, X., Ma, L., Dai, L., Zuo, D., Li, X., Zhu, H., Xu, F."TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways". Oncology Reports 44, no. 2 (2020): 577-588. https://doi.org/10.3892/or.2020.7631
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao X, Ma L, Dai L, Zuo D, Li X, Zhu H and Xu F: TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways. Oncol Rep 44: 577-588, 2020.
APA
Zhao, X., Ma, L., Dai, L., Zuo, D., Li, X., Zhu, H., & Xu, F. (2020). TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways. Oncology Reports, 44, 577-588. https://doi.org/10.3892/or.2020.7631
MLA
Zhao, X., Ma, L., Dai, L., Zuo, D., Li, X., Zhu, H., Xu, F."TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways". Oncology Reports 44.2 (2020): 577-588.
Chicago
Zhao, X., Ma, L., Dai, L., Zuo, D., Li, X., Zhu, H., Xu, F."TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways". Oncology Reports 44, no. 2 (2020): 577-588. https://doi.org/10.3892/or.2020.7631
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