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Updated: Mar 15, 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

14.7K

PARP3 controls TGFβ and ROS driven epithelial-to-mesenchymal transition and stemness by stimulating a

Olga Karicheva1, José Manuel Rodriguez-Vargas1, Nadège Wadier1

  • 1Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, UMR7242, Centre National de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 67412 Illkirch, France.

Oncotarget
|September 1, 2016
PubMed

Insights

Poly(ADP-ribose) polymerase 3 (PARP3) is crucial for epithelial-to-mesenchymal transition (EMT) and stem-like properties in breast cancer cells. PARP3 promotes EMT by regulating key molecular axes and enhances cancer stem cell characteristics.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Poly(ADP-ribose) polymerase (PARP) family members are key in genome integrity and cancer drug development.
  • PARP3 is known for its roles in DNA repair and mitosis.
  • The function of PARP3 in epithelial-to-mesenchymal transition (EMT) and stemness remains largely unexplored.

Purpose of the Study:

  • To investigate the role of PARP3 in TGFβ and reactive oxygen species (ROS)-induced EMT.
  • To determine PARP3's involvement in the development of stem-like cell properties in breast cancer.
  • To explore the therapeutic potential of targeting PARP3 in cancer.

Main Methods:

  • Analysis of PARP3 expression in breast cancer cell lines with different phenotypes.
  • Induction of EMT using TGFβ and assessment of PARP3 expression.
  • Depletion of PARP3 using siRNA and evaluation of EMT markers and processes.
  • Assessment of stem-like cell properties, including marker expression and spheroid formation.

Main Results:

  • PARP3 expression is elevated in mesenchymal breast cancer cells and inversely correlates with E-cadherin, positively with Vimentin.
  • PARP3 is upregulated during TGFβ-induced EMT and is essential for TGFβ-dependent EMT progression.
  • PARP3 depletion inhibits EMT by affecting the Snail-E-cadherin axis, cell junctions, motility, and chemoresistance.
  • PARP3 promotes stem-like properties by upregulating SOX2 and OCT4, increasing CD44high/CD24low population, and enhancing spheroid formation.

Conclusions:

  • PARP3 plays a significant role in regulating TGFβ-induced EMT and stem-like cell characteristics in mammary epithelial and breast cancer cells.
  • PARP3 acts through a TG2-Snail-E-cadherin axis, modulated by ROS, during EMT.
  • These findings highlight PARP3 as a novel therapeutic target for inhibiting EMT and cancer stemness.
Keywords:
EMTPoly(ADP-ribose) polymerase 3 (PARP3)ROSTGFβstem cells

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