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Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
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FHIT suppresses cervical squamous cell carcinoma progression by negatively regulating UBE2I-mediated SUMO

Shunjie Zheng1, Fulei Shao2, Liujuan Shao1

  • 1Department of Gynecology, Jinhua Maternal and Child Health Care Hospital, Jinhua 321000, Zhejiang, China.

Cellular Signalling
|May 12, 2026
PubMed
Abstract

Insights

The fragile histidine triad (FHIT) gene suppresses tumors in cervical squamous cell carcinoma (CSCC). Restoring FHIT inhibits cancer growth and promotes anti-tumor immune responses by targeting the UBE2I/NOTCH1 pathway.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Fragile histidine triad (FHIT) acts as a tumor suppressor, often silenced by promoter hypermethylation in various cancers.
  • FHIT silencing is prevalent in cervical squamous cell carcinoma (CSCC), suggesting a role in its pathogenesis.

Purpose of the Study:

  • To investigate the role of FHIT in CSCC progression and immunoregulation.
  • To identify the downstream molecular mechanisms underlying FHIT's function in CSCC.

Main Methods:

  • Analysis of GEO and TCGA datasets for FHIT expression and methylation in CSCC.
  • Validation using RT-qPCR, MSP-PCR, and Western blot in CSCC cell lines.
  • Gain- and loss-of-function studies to assess FHIT's impact on proliferation, metastasis, and macrophage polarization.

Main Results:

  • FHIT was found to be hypermethylated and downregulated in CSCC.
  • FHIT overexpression suppressed CSCC cell proliferation, migration, and invasion.
  • FHIT-overexpressing CSCC cells enhanced M1 macrophage polarization.
  • FHIT targets UBE2I, which mediates SUMO modification of NOTCH1 at K1607, influencing oncogenesis.

Conclusions:

  • FHIT exhibits antitumor properties in CSCC by inhibiting proliferation and metastasis.
  • The FHIT/UBE2I/NOTCH1 axis plays a crucial role in CSCC development and immunoregulation.
  • Targeting the FHIT/UBE2I/NOTCH1 pathway offers a potential immunomodulatory therapeutic strategy for CSCC.
Keywords:
Cervical squamous cell carcinomaFHITMacrophagesSUMO modificationUBE2I

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