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

Autor:	Liu H; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Xiang Y; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Zong QB; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Dai ZT; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Wu H; Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China., Zhang HM; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Huang Y; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Shen C; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Wang J; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Lu ZX; Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China., Ponnambalam S; School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK., Chen K; School of Medicine, Liaocheng University, Liaocheng, Shandong 252000, P.R. China., Wu Y; Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China., Zhang TC; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China., Liao XH; Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China.
Jazyk:	angličtina
Zdroj:	International journal of oncology [Int J Oncol] 2022 Jun; Vol. 60 (6). Date of Electronic Publication: 2022 Apr 27.
DOI:	10.3892/ijo.2022.5362
Abstrakt:	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.
Databáze:	MEDLINE
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