APC senses cell-cell contacts and moves to the nucleus upon their disruption

M G Brocardo1, M Bianchini, M Radrizzani

  • 1Instituto de Investigaciones Bioquímicas Fundación Campomar (IIBBA-CONICET, IIB-Universidad de Buenos Aires), Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.

Insights

The adenomatous polyposis coli (APC) protein moves to the nucleus when cell contacts are lost and returns to the cytoplasm when cell contacts are restored. This suggests APC acts as a sensor for cell-cell adhesion.

Area of Science:

  • Cell biology
  • Molecular biology
  • Cancer research

Background:

  • The adenomatous polyposis coli (APC) protein is a key regulator of the Wnt/beta-catenin signaling pathway.
  • APC's role in cell-cell adhesion and its dynamic localization are not fully understood.

Purpose of the Study:

  • To develop a specific reagent to study APC localization.
  • To investigate the dynamic changes in APC protein localization in response to cell-cell contact disruption and reestablishment.

Main Methods:

  • Chemical synthesis of an oligobody (oligonucleotide-based synthetic antibody) targeting the N-terminal region of APC.
  • Treatment of HT-29 cells with trypsin/EDTA to disrupt cell-cell contacts.
  • Observation of APC localization using the synthesized oligobody after cell replating and confluence.

Main Results:

  • A highly specific oligobody targeting APC was successfully developed.
  • Disruption of cell-cell contacts induced rapid translocation of APC from the cytoplasm to the nucleus within 16 hours.
  • Upon reestablishment of cell-cell contacts after 5 days, APC returned to the cytoplasm.

Conclusions:

  • APC protein localization is sensitive to the state of cell-cell contacts.
  • APC may function as a "sensor" that responds to changes in cell adhesion by altering its subcellular localization.
  • These findings provide new insights into the dynamic regulation of APC in cellular processes.

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