A positive feedback loop between tryptophan hydroxylase 1 and beta-Catenin/ZBP-89 signaling promotes prostate cancer progression

作者全名："Ge, Chengguo; Yan, Jiusong; Yuan, Xiaoyu; Xu, Guangyong"

作者地址："[Ge, Chengguo; Yan, Jiusong; Yuan, Xiaoyu; Xu, Guangyong] Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, Chongqing, Peoples R China"

通信作者："Xu, GY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000860786100001

JCR分区：Q2

影响因子：4.7

年份：2022

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：tryptophan hydroxylase 1; 5-hydroxytryptamine; beta-catenin; ZBP-89; prostate cancer

摘要："Alterations in tryptophan (Trp) metabolism facilitate the continuous modulation of tumor progression, including tumor growth, distant metastasis, and chemoresistance development. Although there is a high correlation between Trp metabolism and tumor progression, it is unknown whether and how Trp metabolism affects the development of prostate cancer. In this study, we reported that the overexpression of Trp hydroxylase 1 (TPH1) caused the upregulation of Trp hydroxylation and mediated the production of 5-hydroxytryptamine (5-HT), contributing to tumor growth and poor prognosis in patients with prostate cancer. An increase in 5-HT levels triggered the activation of the Axin 1/beta-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, beta-catenin cooperated with the Kruppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/beta-catenin/ZBP-89/THP1 positive feedback signaling loop. Interruption of the signaling loop by the THP1 inhibitor 4-chloro-dl-phenylalanine (PCPA) significantly improved anticancer effects and suppressed lung metastasis in prostate cancer-bearing mice. Our findings revealed a mechanism by which TPH1 promotes prostate cancer growth by inducing Trp hydroxylation and identified a novel THP1 target for an innovative prostate cancer therapeutic strategy."

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