HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis
Abstract Accumulating evidence shows HOOK1 disordered in human malignancies. However, the clinicopathological and biological significance of HOOK1 in renal cell carcinoma (RCC) remains rarely studied. In this study, the authors demonstrate that HOOK1 is downregulated in RCC samples with predicted po...
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202206955 |
| _version_ | 1797804425147842560 |
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| author | Lei Yin Wenjia Li Xuxiao Chen Ronghao Wang Tao Zhang Jialin Meng Zhao Li Li Xu Rui Yin Bo Cheng Huan Yang |
| author_facet | Lei Yin Wenjia Li Xuxiao Chen Ronghao Wang Tao Zhang Jialin Meng Zhao Li Li Xu Rui Yin Bo Cheng Huan Yang |
| author_sort | Lei Yin |
| collection | DOAJ |
| description | Abstract Accumulating evidence shows HOOK1 disordered in human malignancies. However, the clinicopathological and biological significance of HOOK1 in renal cell carcinoma (RCC) remains rarely studied. In this study, the authors demonstrate that HOOK1 is downregulated in RCC samples with predicted poorer clinical prognosis. Mechanistically, HOOK1 inhibits tumor growth and metastasis via canonical TGF‐β/ALK5/p‐Smad3 and non‐canonical TGF‐β/MEK/ERK/c‐Myc pathway. At the same time, HOOK1 inhibits RCC angiogenesis and sunitinib resistance by promoting degradation of TNFSF13B through the ubiquitin‐proteasome pathway. In addition, HOOK1 is transcriptionally regulated by nuclear factor E2F3 in VHL dependent manner. Notably, an agonist of HOOK1, meletin, is screened and it shows antitumor activity more effectively when combined with sunitinib or nivolumab than it is used alone. The findings reveal a pivotal role of HOOK1 in anti‐cancer treatment, and identify a novel therapeutic strategy for renal cell carcinoma. |
| first_indexed | 2024-03-13T05:36:57Z |
| format | Article |
| id | doaj.art-dc1a1e76464d4fbf837435e975ae41e0 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T05:36:57Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-dc1a1e76464d4fbf837435e975ae41e02023-06-14T07:18:56ZengWileyAdvanced Science2198-38442023-06-011017n/an/a10.1002/advs.202206955HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A AxisLei Yin0Wenjia Li1Xuxiao Chen2Ronghao Wang3Tao Zhang4Jialin Meng5Zhao Li6Li Xu7Rui Yin8Bo Cheng9Huan Yang10Department of Urology Putuo People's Hospital Tongji University Shanghai 200060 P. R. ChinaDepartment of Cardiovascular Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. ChinaDepartment of General Surgery Hepatobiliary Surgery Shanghai Institute of Digestive Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. ChinaDepartment of Biochemistry and Molecular Biology School of Basic Medical Sciences Southwest Medical University Luzhou 646000 P. R. ChinaDepartment of Urology Putuo People's Hospital Tongji University Shanghai 200060 P. R. ChinaDepartment of Urology The First Affiliated Hospital of Anhui Medical University Anhui Province Key Laboratory of Genitourinary Diseases Anhui Medical University Hefei 230032 P. R. ChinaDepartment of Anesthesiology Xiangya Hospital Central South University Changsha 410008 P. R. ChinaDepartment of Anesthesiology The First People's Hospital of Changde Changde 415000 P. R. ChinaCenter for Reproductive Medicine Shandong University Jinan 250012 P. R. ChinaDepartment of Urology The Affiliated Hospital of Southwest Medical University Luzhou 646000 P. R. ChinaDepartment of Urology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030 P. R. ChinaAbstract Accumulating evidence shows HOOK1 disordered in human malignancies. However, the clinicopathological and biological significance of HOOK1 in renal cell carcinoma (RCC) remains rarely studied. In this study, the authors demonstrate that HOOK1 is downregulated in RCC samples with predicted poorer clinical prognosis. Mechanistically, HOOK1 inhibits tumor growth and metastasis via canonical TGF‐β/ALK5/p‐Smad3 and non‐canonical TGF‐β/MEK/ERK/c‐Myc pathway. At the same time, HOOK1 inhibits RCC angiogenesis and sunitinib resistance by promoting degradation of TNFSF13B through the ubiquitin‐proteasome pathway. In addition, HOOK1 is transcriptionally regulated by nuclear factor E2F3 in VHL dependent manner. Notably, an agonist of HOOK1, meletin, is screened and it shows antitumor activity more effectively when combined with sunitinib or nivolumab than it is used alone. The findings reveal a pivotal role of HOOK1 in anti‐cancer treatment, and identify a novel therapeutic strategy for renal cell carcinoma.https://doi.org/10.1002/advs.202206955HOOK1renal cell carcinomaTGF‐Î2 signalingTNFSF13Btumor metastasis |
| spellingShingle | Lei Yin Wenjia Li Xuxiao Chen Ronghao Wang Tao Zhang Jialin Meng Zhao Li Li Xu Rui Yin Bo Cheng Huan Yang HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis Advanced Science HOOK1 renal cell carcinoma TGF‐Î2 signaling TNFSF13B tumor metastasis |
| title | HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis |
| title_full | HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis |
| title_fullStr | HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis |
| title_full_unstemmed | HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis |
| title_short | HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis |
| title_sort | hook1 inhibits the progression of renal cell carcinoma via tgf β and tnfsf13b vegf a axis |
| topic | HOOK1 renal cell carcinoma TGF‐Î2 signaling TNFSF13B tumor metastasis |
| url | https://doi.org/10.1002/advs.202206955 |
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