journal article·2023-06Open access

HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF‐β and TNFSF13B/VEGF‐A Axis

Lei Yin, Wenjia Li, Xuxiao Chen, Ronghao Wang, Tao Zhang, Jialin Meng, Zhao Li, Li Xu, Rui Yin, Bo Cheng, Huan Yang

Advanced Science· Volume 10· Issue 17

Abstract

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.
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Research context

OpenAlex topics: Cancer, Hypoxia, and Metabolism · Cancer, Lipids, and Metabolism · Angiogenesis and VEGF in Cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Urology Putuo People's Hospital Tongji University Shanghai 200060 P. R. China

Department of Urology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China

Department of Cardiovascular Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China

Department of General Surgery Hepatobiliary Surgery Shanghai Institute of Digestive Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China

Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southwest Medical University Luzhou 646000 P. R. China

Department of Urology The First Affiliated Hospital of Anhui Medical University Anhui Province Key Laboratory of Genitourinary Diseases Anhui Medical University Hefei 230032 P. R. China

Department of Anesthesiology Xiangya Hospital Central South University Changsha 410008 P. R. China

Department of Anesthesiology The First People's Hospital of Changde Changde 415000 P. R. China

Center for Reproductive Medicine Shandong University Jinan 250012 P. R. China

Department of Urology The Affiliated Hospital of Southwest Medical University Luzhou 646000 P. R. China

Department of Urology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030 P. R. China

Funding

National Natural Science Foundation of China

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