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RING1 is an Integrin α5 E3 ubiquitin ligase and inhibits esophageal squamous cell carcinoma cell migration and

Jingya Guo1, Yanlin Zhao2, Yan Sun3

  • 1Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225000, China; Department of Clinical Medicine, Faculty of Medicine, Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control, Yangzhou University, Yangzhou, Jiangsu 225001, China.

Cellular Signalling
|June 2, 2026
PubMed

Insights

Ring finger protein 1 (RING1) inhibits esophageal squamous cell carcinoma (ESCC) metastasis by targeting Integrin α5. This discovery reveals a new therapeutic target for treating metastatic ESCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, largely due to metastasis.
  • Cell migration is a key driver of ESCC metastasis.
  • The role of Ring finger protein 1 (RING1) in ESCC metastasis is not fully understood.

Purpose of the Study:

  • To investigate the function and mechanism of RING1 in ESCC cell migration and metastasis.
  • To identify substrates of RING1 involved in ESCC progression.

Main Methods:

  • Cell migration, adhesion, and spreading assays.
  • Western blotting and ubiquitination assays.
  • Overexpression and knockdown studies in ESCC cell lines.
  • Analysis of the Integrin α5/FAK signaling pathway.

Main Results:

  • RING1 inhibits ESCC cell migration, adhesion, and spreading in a catalytic domain-dependent manner.
  • RING1 targets Integrin α5 for degradation via K11-linked ubiquitination.
  • Overexpression of RING1 suppresses metastasis, while Integrin α5 re-expression or knockdown abrogates these effects.
  • RING1 regulates the Integrin α5/FAK pathway.

Conclusions:

  • RING1 acts as a tumor suppressor in ESCC by inhibiting cell migration and metastasis.
  • Integrin α5 is a novel substrate of RING1, and their interaction is crucial for controlling ESCC cell behavior.
  • The RING1/Integrin α5/FAK axis represents a potential therapeutic target for metastatic ESCC.
Keywords:
Cell adhesionCell migrationEsophageal squamous cell carcinomaIntegrin α5MetastasisRing finger protein 1Ubiquitination

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