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Updated: Jun 11, 2025

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Translation Initiation Factor-2S2 (eIF2S2) Contributes to Cervical Carcinogenesis by Inhibiting the TGF-β/SMAD4

Juthika Kundu1, Hobin Yang2, Saerom Moon3

  • 1Lika shing applied virology institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.

Biomolecules & Therapeutics
|October 7, 2024
PubMed

Insights

Eukaryotic translation initiation factor 2S2 (eIF2S2) promotes cervical cancer growth and migration. This factor interacts with SMAD4, reducing its expression and the activity of tumor-suppressing proteins p15 and p27.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Deregulation of protein translation is implicated in cancer.
  • The role of translation initiation factors in cervical carcinogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of eukaryotic translation initiation factor 2S2 (eIF2S2) in cervical cancer.
  • To elucidate the molecular mechanisms underlying eIF2S2's function in cervical carcinogenesis.

Main Methods:

  • Immunohistochemical analysis of cervical carcinoma tissues.
  • Cell-based assays including knockdown and overexpression of eIF2S2 in SiHa cells.
  • Immunoprecipitation and Bimolecular fluorescence complementation (BiFC) assays to study protein interactions.

Main Results:

  • eIF2S2 expression increased with cervical cancer stage.
  • eIF2S2 knockdown inhibited cancer cell growth and migration; overexpression enhanced these properties.
  • eIF2S2 directly interacts with SMAD4, affecting its post-translational regulation.
  • eIF2S2 overexpression reduced SMAD4 levels, subsequently decreasing the expression and promoter activity of antiproliferative proteins p15 and p27.

Conclusions:

  • eIF2S2 plays a pro-tumorigenic role in cervical carcinogenesis.
  • eIF2S2 diminishes SMAD4 expression and its function as a transcriptional factor, contributing to tumor development.
Keywords:
CarcinogenesisCervical cancerSMAD4TGF-βeIF2S2

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