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Updated: May 9, 2026
08:13
Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
Published on: September 26, 2025
Novel small-molecule compounds that affect cellular morphogenesis in yeast and mammalian cells
Tomoaki Fukunaga1, Mikiko Nakamura, Takao Kitagawa
1Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine.
Bioscience, Biotechnology, and Biochemistry
|August 9, 2013
Summary
Researchers screened 8000 compounds to find drugs that alter cell shape, potentially treating cancer metastasis. This study identified small molecules affecting yeast and human cell morphology, offering new therapeutic avenues for actin-related diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Targeting cellular morphological changes is crucial for developing anti-cancer therapies, particularly for inhibiting tumor cell migration and invasion.
- The yeast formin protein Bni1 and Src homology 3 (SH3)-pleckstrin homology (PH) domain protein Boi1 are essential for cell morphogenesis and cause growth defects when overexpressed.
- Identifying small-molecule compounds that modulate these cellular processes can lead to novel therapeutic agents.
Purpose of the Study:
- To screen a chemical library of approximately 8000 compounds to identify drug candidates that affect cellular morphology in both yeast and mammalian HEK293 cells.
- To identify compounds that suppress growth defects caused by the overexpression of Bni1 and Boi1 in yeast.
- To evaluate the potential of identified compounds as therapeutic drugs for cancer metastasis and other actin-related diseases.
Main Methods:
- Utilized a yeast-based screening system involving the overexpression of Bni1 and Boi1 to identify compounds suppressing associated growth defects.
- Screened a chemical library of ~8000 small-molecule compounds.
- Assessed the effects of identified compounds on cellular morphology in both unicellular yeast and mammalian HEK293 cells, including their impact on actin localization and projection formation.
- Investigated the differential effects of structurally similar compounds (BTB03156 and BTB02467) on yeast growth defects induced by latrunculin A, an actin polymerization inhibitor.
Main Results:
- No screened compounds induced morphological changes in vegetatively growing yeast cells.
- Several compounds exhibited inhibitory effects on pheromone-induced projection formation and actin localization in yeast, indicating specific effects on morphogenesis.
- Five compounds induced morphological changes in mammalian HEK293 cells.
- Two identified compounds, BTB03156 and BTB02467, despite structural similarities, showed distinct effects on yeast growth defects caused by latrunculin A.
Conclusions:
- The in vivo screening approach successfully identified simple, cell-permeable small-molecule compounds that modulate cellular morphology.
- The identified compounds demonstrate potential utility in developing therapeutic drugs targeting cancer metastasis and other actin-related diseases.
- The differential effects of structurally similar compounds highlight the specificity of their mechanisms of action.
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