A vimentin binding small molecule leads to mitotic disruption in mesenchymal cancers

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Updated: Feb 19, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Michael J Bollong1, Mika Pietilä2, Aaron D Pearson1

  • 1Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.

Proceedings of the National Academy of Sciences of the United States of America
|November 1, 2017
PubMed

Insights

A new drug, FiVe1, stops the growth of mesenchymal cancer cells by targeting the vimentin protein. This molecule disrupts cell division, offering a potential therapy for metastatic cancers and those resistant to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for cancer metastasis and stemness.
  • FOXC2 transcription factor drives EMT and is a target for cancer therapies.
  • Inhibiting FOXC2-driven cancers may overcome chemotherapy resistance and metastasis.

Purpose of the Study:

  • Identify agents that inhibit FOXC2-transformed cancer cell growth.
  • Explore novel therapeutic strategies against metastatic and chemotherapy-resistant cancers.
  • Investigate the mechanism of action for novel anti-cancer compounds.

Main Methods:

  • High-throughput synthetic lethal screening to identify growth inhibitors.
  • Small molecule screening using mesenchymally transformed breast cancer cells and sarcomas.
  • Analysis of vimentin (VIM) targeting and its effects on cell mitosis and stemness.

Main Results:

  • FiVe1, a small molecule, selectively and irreversibly inhibits growth of mesenchymal cancer cells.
  • FiVe1 targets vimentin (VIM), causing its disorganization and phosphorylation during metaphase.
  • Observed effects include mitotic catastrophe, multinucleation, and loss of cancer stemness.

Conclusions:

  • FiVe1 represents a novel therapeutic agent for mesenchymal cancers.
  • Disruption of vimentin dynamics offers a new strategy to halt mitotic progression.
  • Findings may guide the development of therapies for diverse mesenchymal cancers.
Keywords:
cancer stem celldrug discoveryepithelial-to-mesenchymal transitionmitosisvimentin

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