A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression
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 meta...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.923307/full |
| _version_ | 1811209662004985856 |
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| author | Chengguo Ge Jiusong Yan Xiaoyu Yuan Guangyong Xu |
| author_facet | Chengguo Ge Jiusong Yan Xiaoyu Yuan Guangyong Xu |
| author_sort | Chengguo Ge |
| collection | DOAJ |
| description | 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/β-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, β-catenin cooperated with the Krüppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/β-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. |
| first_indexed | 2024-04-12T04:44:19Z |
| format | Article |
| id | doaj.art-1584053eb83442488e1e26306853c54d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T04:44:19Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1584053eb83442488e1e26306853c54d2022-12-22T03:47:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.923307923307A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progressionChengguo GeJiusong YanXiaoyu YuanGuangyong XuAlterations 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/β-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, β-catenin cooperated with the Krüppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/β-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.https://www.frontiersin.org/articles/10.3389/fonc.2022.923307/fulltryptophan hydroxylase 15-hydroxytryptaminebeta-cateninZBP-89prostate cancer |
| spellingShingle | Chengguo Ge Jiusong Yan Xiaoyu Yuan Guangyong Xu A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression Frontiers in Oncology tryptophan hydroxylase 1 5-hydroxytryptamine beta-catenin ZBP-89 prostate cancer |
| title | A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression |
| title_full | A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression |
| title_fullStr | A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression |
| title_full_unstemmed | A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression |
| title_short | A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression |
| title_sort | positive feedback loop between tryptophan hydroxylase 1 and β catenin zbp 89 signaling promotes prostate cancer progression |
| topic | tryptophan hydroxylase 1 5-hydroxytryptamine beta-catenin ZBP-89 prostate cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.923307/full |
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