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Updated: Oct 26, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
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Isorhapontigenin (ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells

Ning Zhang1, Xiaohui Hua2, Huailu Tu1

  • 1Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25th Street, New York, NY, 10010, USA.

Cancer Letters
|July 31, 2021
PubMed

Insights

Isoflavone (ISO) inhibits bladder cancer cell invasion by reducing Vimentin, a key marker of epithelial mesenchymal transition (EMT). This occurs through upregulation of METTL14 via the FOXO3a pathway, offering new therapeutic insights.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Epithelial mesenchymal transition (EMT) is crucial for cancer metastasis.
  • Isoflavone (ISO) is known to inhibit cancer cell invasion and stem-cell properties.
  • The effect of ISO on EMT markers remains largely unexplored.

Purpose of the Study:

  • To investigate the regulatory role of ISO on EMT in bladder cancer.
  • To determine if ISO affects EMT markers, leading to reduced migration and invasion.
  • To elucidate the molecular mechanisms underlying ISO's effects on bladder cancer cells.

Main Methods:

  • Utilized invasive bladder cancer cell lines (U5637 and T24T).
  • Assessed the protein and mRNA levels of EMT markers, specifically Vimentin.
  • Investigated the expression of METTL14 and the transcription factor FOXO3a.
  • Analyzed the regulatory pathways connecting ISO, FOXO3a, METTL14, and Vimentin.

Main Results:

  • ISO significantly inhibited Vimentin protein levels in bladder cancer cells.
  • ISO treatment led to increased expression of METTL14.
  • ISO upregulated METTL14 mRNA by activating the transcription factor FOXO3a.
  • These molecular changes correlated with reduced cancer cell invasion and migration.

Conclusions:

  • ISO effectively inhibits bladder cancer cell invasion by modulating EMT markers.
  • ISO upregulates METTL14 expression through the FOXO3a pathway, impacting Vimentin levels.
  • This study provides novel insights into the anti-metastatic potential of ISO via EMT regulation.
Keywords:
EMTFOXO3aISOMETTL14Vimentin

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