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PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position

Pablo Luján1, Giulia Varsano1, Teresa Rubio1

  • 1European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.

Journal of Cell Science
|September 23, 2016
PubMed

Insights

The phosphatase PRL-3 (PTP4A3) promotes cancer by disrupting epithelial architecture. It causes cells to form multiple lumens, a key cancer hallmark, by accelerating cell division.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Epithelial Biology

Background:

  • Epithelial architecture disruption is crucial in cancer development.
  • PRL-3 (PTP4A3) is a phosphatase overexpressed in various epithelial cancers.
  • Ectopic lumen formation is a hallmark of cancer progression.

Purpose of the Study:

  • To investigate the role of PRL-3 (PTP4A3) in disrupting epithelial architecture.
  • To elucidate the mechanism by which PRL-3 promotes ectopic lumen formation.
  • To validate the role of PRL-3 in breast cancer cell models.

Main Methods:

  • Expression of PRL-3 in polarized epithelial cells (MDCK, Caco2) and analysis of cyst formation.
  • Knockdown of endogenous PRL-3 in MCF-7 breast cancer cells cultured in 3D structures.
  • Microscopic analysis of cell division, spindle orientation, and midbody localization.

Main Results:

  • PRL-3 expression induced cell invasion and formation of multiple ectopic lumens in epithelial cysts.
  • Knockdown of PRL-3 reversed multiple-lumen formation to single-lumen structures in breast cancer cells.
  • PRL-3 accelerated cytokinesis, leading to midbody mispositioning and ectopic lumen formation without affecting spindle orientation or abscission.

Conclusions:

  • PRL-3 (PTP4A3) disrupts epithelial architecture, promoting cancer progression through a novel mechanism.
  • PRL-3-induced ectopic lumen formation occurs via accelerated cytokinesis and midbody mispositioning.
  • Targeting PRL-3 may offer a therapeutic strategy for epithelial cancers.
Keywords:
CancerCell polarityEpitheliaMidbodyPRL-3PTP4A3

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