The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis
Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SP...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.658230/full |
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| author | Jinlu Ma Jinlu Ma Mengjiao Cai Yaqi Mo Joshua S. Fried Xinyue Tan Yuan Ma Jie Chen Suxia Han Bo Xu Bo Xu |
| author_facet | Jinlu Ma Jinlu Ma Mengjiao Cai Yaqi Mo Joshua S. Fried Xinyue Tan Yuan Ma Jie Chen Suxia Han Bo Xu Bo Xu |
| author_sort | Jinlu Ma |
| collection | DOAJ |
| description | Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis. |
| first_indexed | 2024-12-20T01:58:20Z |
| format | Article |
| id | doaj.art-00370619e550443d8f182bc7970ccc03 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T01:58:20Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-00370619e550443d8f182bc7970ccc032022-12-21T19:57:24ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.658230658230The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer MetastasisJinlu Ma0Jinlu Ma1Mengjiao Cai2Yaqi Mo3Joshua S. Fried4Xinyue Tan5Yuan Ma6Jie Chen7Suxia Han8Bo Xu9Bo Xu10Department of Radiation Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Oncology, Southern Research Institute, and University Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Radiation Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDepartment of Oncology, Southern Research Institute, and University Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Radiation Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Radiation Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Oncology, Southern Research Institute, and University Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Radiation Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaCenter for Intelligent Oncology, Chongqing University Cancer Hospital and Chongqing University School of Medicine, Chongqing, ChinaProstate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.https://www.frontiersin.org/articles/10.3389/fonc.2021.658230/fullSPOPubiquitylationprostate cancerITCHmetastasis |
| spellingShingle | Jinlu Ma Jinlu Ma Mengjiao Cai Yaqi Mo Joshua S. Fried Xinyue Tan Yuan Ma Jie Chen Suxia Han Bo Xu Bo Xu The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis Frontiers in Oncology SPOP ubiquitylation prostate cancer ITCH metastasis |
| title | The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis |
| title_full | The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis |
| title_fullStr | The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis |
| title_full_unstemmed | The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis |
| title_short | The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis |
| title_sort | spop itch signaling axis protects against prostate cancer metastasis |
| topic | SPOP ubiquitylation prostate cancer ITCH metastasis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.658230/full |
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