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Updated: Jan 30, 2026
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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PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells
Michelle Schacke1, Janani Kumar2, Nicholas Colwell3
1Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay. asistentes@iibce.edu.uy.
International Journal of Molecular Sciences
|January 30, 2019
Summary
Poly (ADP-ribose) (PAR) levels and distribution change during cancer cell Epithelial-Mesenchymal Transition (EMT). The PARP inhibitor Olaparib (OLA) prevents and reverses EMT, suggesting novel therapeutic strategies beyond synthetic lethality.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Poly (ADP-ribose) (PAR) is a posttranslational modification synthesized by poly (ADP-ribose) polymerases (PARPs).
- PARP alterations are implicated in cancer, potentially by influencing Epithelial-Mesenchymal Transition (EMT), a process critical for cancer cell migration and drug resistance.
- The PARP inhibitor Olaparib (OLA) is an FDA-approved treatment for specific cancers with homologous recombination deficiencies.
Purpose of the Study:
- To investigate PAR changes during EMT.
- To determine the effects of Olaparib (OLA) on EMT.
- To explore potential unconventional mechanisms of action for OLA in cancer treatment.
Main Methods:
- Immuno-cytofluorescence and image quantification to assess molecular markers.
- Western blots and RNA quantitation to analyze protein and gene expression.
- Scratch assays to evaluate cell migration capacity and morphological changes (anisotropy).
Main Results:
- Total and nuclear PAR levels increased during EMT, while PAR belts disassembled.
- OLA treatment prevented EMT, as evidenced by molecular markers, morphological changes, and reduced migration.
- OLA also demonstrated a partial reversal of EMT.
Conclusions:
- PAR dynamics are altered during EMT.
- OLA effectively inhibits EMT, irrespective of BRCA mutation status.
- OLA may exert anti-cancer effects through mechanisms beyond synthetic lethality, offering potential for broader therapeutic applications.
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