Related Experiment Video

Updated: Aug 2, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF-β and TNFSF13B/VEGF-A Axis

Lei Yin1,2, Wenjia Li3, Xuxiao Chen4

  • 1Department of Urology, Putuo People's Hospital, Tongji University, Shanghai, 200060, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 21, 2023
PubMed

Insights

HOOK1, a gene downregulated in renal cell carcinoma (RCC), inhibits tumor growth and metastasis. Targeting HOOK1 with agonists like meletin offers a novel therapeutic strategy for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • HOOK1 is implicated in human malignancies but its role in renal cell carcinoma (RCC) is understudied.
  • Understanding HOOK1's function in RCC is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the clinicopathological and biological significance of HOOK1 in renal cell carcinoma (RCC).
  • To elucidate the mechanisms by which HOOK1 affects RCC progression and treatment response.

Main Methods:

  • Analysis of HOOK1 expression in RCC samples and correlation with clinical prognosis.
  • Investigation of HOOK1's role in tumor growth, metastasis, and angiogenesis.
  • Exploration of HOOK1's regulation by E2F3 and VHL.
  • Screening of HOOK1 agonists and evaluation of their efficacy in combination therapies.

Main Results:

  • HOOK1 is downregulated in RCC, correlating with poorer prognosis.
  • HOOK1 suppresses RCC growth and metastasis via TGF-β/ALK5/p-Smad3 and TGF-β/MEK/ERK/c-Myc pathways.
  • HOOK1 inhibits angiogenesis and sunitinib resistance by promoting TNFSF13B degradation.
  • HOOK1 is regulated by E2F3 in a VHL-dependent manner.
  • Meletin, a HOOK1 agonist, shows enhanced antitumor activity with sunitinib or nivolumab.

Conclusions:

  • HOOK1 plays a critical role in suppressing renal cell carcinoma progression.
  • HOOK1 downregulation contributes to RCC aggressiveness and therapeutic resistance.
  • Meletin, in combination with existing therapies, represents a promising novel therapeutic strategy for RCC.
Keywords:
HOOK1TGF-Î2 signalingTNFSF13Brenal cell carcinomatumor metastasis

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