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Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
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The adherens junction protein afadin is an AKT substrate that regulates breast cancer cell migration

Sivan Elloul1, Dmitriy Kedrin, Nicholas W Knoblauch

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115. atoker@bidmc.harvard.edu.

Molecular Cancer Research : MCR
|November 26, 2013
PubMed
Abstract

Insights

The PI3K-AKT pathway regulates cancer progression. AKT phosphorylates Afadin, causing it to move to the nucleus and increase breast cancer cell migration.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Signaling

Background:

  • The PI3K-AKT pathway is crucial for human cancer progression, including breast cancer.
  • AKT phosphorylates substrates involved in cell growth, survival, migration, and invasion.

Purpose of the Study:

  • To identify new AKT substrates involved in cancer progression.
  • To investigate the role of Afadin phosphorylation by AKT in breast cancer.

Main Methods:

  • Identification of Afadin as a novel AKT substrate phosphorylated at Ser1718.
  • Analysis of Afadin relocalization upon AKT activation under various signaling conditions.
  • Assessment of Afadin phosphorylation's impact on breast cancer cell migration.
  • Examination of Afadin nuclear localization in clinical breast cancer samples.

Main Results:

  • Afadin is phosphorylated by AKT at Ser1718, leading to its nuclear relocalization.
  • This phosphorylation event enhances breast cancer cell migration in a Ser1718-dependent manner.
  • Nuclear localization of Afadin was confirmed in clinical breast cancer specimens.

Conclusions:

  • Phosphorylation of Afadin by AKT, a key event in the PI3K-AKT pathway, drives breast cancer cell migration.
  • The PI3K-AKT-Afadin axis represents a significant pathway in breast cancer pathophysiology.

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