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Ezrin-radixin-moesin-binding phosphoprotein-50 regulates EGF-induced AKT activation through interaction with EGFR and

Junfang Zheng1, Yuanping Dai1, Zhiyu Yang1

  • 1Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, P.R. China.

Oncology Reports
|November 5, 2015
PubMed

Insights

Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) mediates the formation of a phosphatase and tensin homolog deleted on chromosome ten (PTEN)/epidermal growth factor receptor (EGFR) complex. This complex effectively inhibits AKT pathway activation, offering a new target for cancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Dysregulated epidermal growth factor receptor (EGFR) signaling, particularly EGFR/AKT, drives tumorigenesis.
  • Phosphatase and tensin homolog deleted on chromosome ten (PTEN) antagonizes AKT activity.
  • Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) may mediate PTEN/EGFR complex formation to regulate signaling.

Purpose of the Study:

  • To investigate the role of EBP50 in mediating the formation of a PTEN/EGFR complex.
  • To determine if the PTEN/EGFR complex regulates EGFR/AKT signaling.
  • To explore the potential of this complex as an antineoplastic therapeutic target.

Main Methods:

  • Co-immunoprecipitation assays to detect PTEN/EGFR complex formation.
  • GST pull-down assays to assess EBP50's role in complex formation.
  • Expression of wild-type and mutant PTEN/EGFR proteins in cells.
  • Western blotting to measure AKT activation levels following EGF stimulation.

Main Results:

  • PTEN co-immunoprecipitated with EGFR, confirming complex formation in tissues.
  • EBP50 knockdown decreased, while overexpression increased, PTEN/EGFR complex formation.
  • Mutant PTEN and EGFR proteins that do not bind EBP50 showed reduced complex formation.
  • EBP50-mediated PTEN/EGFR complex formation effectively inhibited EGF-induced AKT activation.

Conclusions:

  • EBP50 specifically mediates the formation of the PTEN/EGFR complex.
  • This complex provides a novel mechanism for negative regulation of EGF-induced AKT signaling.
  • The EBP50-mediated PTEN/EGFR complex represents a potential molecular target for cancer therapy.

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