TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway

  • Authors:
    • Hui Liu
    • Yuan Xiang
    • Qi-Bei Zong
    • Zhou-Tong Dai
    • Hao Wu
    • Hui-Min Zhang
    • You Huang
    • Chao Shen
    • Jun Wang
    • Zhong-Xin Lu
    • Sreenivasan Ponnambalam
    • Kun Chen
    • Yuan Wu
    • Tong-Cun Zhang
    • Xing-Hua Liao
  • View Affiliations

  • Published online on: April 26, 2022     https://doi.org/10.3892/ijo.2022.5362
  • Article Number: 72
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Abstract

Liver cancer is a malignant cancer phenotype for which there currently remains a lack of reliable biomarkers and therapeutic targets for disease management. Tryptophan 2,3‑dioxygenase (TDO2), a heme‑containing polyoxygenase enzyme, is primarily expressed in cells of the liver and nervous systems. In the present study, through the combination of cancer bioinformatics and analysis of clinical patient samples, it was shown that TDO2 expression in liver cancer tissue samples was significantly higher than that in normal tissues, and liver cancer patients with high TDO2 expression had a poor prognosis. Mechanistic studies on liver cancer cells showed that TDO2 promoted cancer cell migration and invasion via signal transduction through the Wnt5a pathway. Such regulation impacted the expression of cancer‑associated biomarkers, such as matrix metalloprotease 7 (MMP7) and the cell adhesion receptor CD44. Treatment with a calcium channel blocker (azelnidipine) reduced TDO2 levels and inhibited liver cancer cell migration and invasion. A mouse xenograft cancer model showed that TDO2 promoted tumorigenesis. Furthermore, azelnidipine treatment to downregulate TDO2 also decreased liver cancer development in this mouse cancer model. TDO2 is thus not only a useful liver cancer biomarker but a potential drug target for management of liver cancer.
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June-2022
Volume 60 Issue 6

Print ISSN: 1019-6439
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Spandidos Publications style
Liu H, Xiang Y, Zong Q, Dai Z, Wu H, Zhang H, Huang Y, Shen C, Wang J, Lu Z, Lu Z, et al: TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway. Int J Oncol 60: 72, 2022
APA
Liu, H., Xiang, Y., Zong, Q., Dai, Z., Wu, H., Zhang, H. ... Liao, X. (2022). TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway. International Journal of Oncology, 60, 72. https://doi.org/10.3892/ijo.2022.5362
MLA
Liu, H., Xiang, Y., Zong, Q., Dai, Z., Wu, H., Zhang, H., Huang, Y., Shen, C., Wang, J., Lu, Z., Ponnambalam, S., Chen, K., Wu, Y., Zhang, T., Liao, X."TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway". International Journal of Oncology 60.6 (2022): 72.
Chicago
Liu, H., Xiang, Y., Zong, Q., Dai, Z., Wu, H., Zhang, H., Huang, Y., Shen, C., Wang, J., Lu, Z., Ponnambalam, S., Chen, K., Wu, Y., Zhang, T., Liao, X."TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway". International Journal of Oncology 60, no. 6 (2022): 72. https://doi.org/10.3892/ijo.2022.5362