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Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
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Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

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P53 mutations in triple negative breast cancer upregulate endosomal recycling of epidermal growth factor receptor

Iuliana Shapira1, Annette Lee, Reena Vora

  • 1Monter Cancer Center, Don Monti Division of Oncology, Division of Hematology, Hofstra North Shore Long Island Jewish School of Medicine, United States.

Critical Reviews in Oncology/Hematology
|June 13, 2013
PubMed

Insights

Targeted therapies for triple-negative breast cancer (TNBC) are lacking. Blocking EGFR signaling and endosomal trafficking, driven by mutant p53, may improve TNBC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) and basal-like breast cancer lack targeted therapies.
  • Epidermal Growth Factor Receptor (EGFR) is overexpressed in TNBC, but anti-EGFR therapies show limited efficacy.
  • Mutant p53, common in aggressive TNBC, influences EGFR signaling and cellular behavior.

Purpose of the Study:

  • To investigate the role of endosomal trafficking in the efficacy of anti-EGFR therapies in TNBC.
  • To elucidate the connection between mutant p53, EGFR signaling, and endosomal trafficking in TNBC.
  • To identify potential combination strategies for improved TNBC treatment.

Main Methods:

  • Analysis of EGFR signaling pathways in TNBC models.
  • Investigation of the interaction between mutant p53 and p63 in regulating endosomal trafficking.
  • Assessment of the impact of blocking endosomal trafficking on EGFR and integrin recycling.
  • Evaluation of combined anti-EGFR and endosomal trafficking inhibition in preclinical models.

Main Results:

  • Increased endosomal recycling of EGFR contributes to the limited success of anti-EGFR therapies in TNBC.
  • Mutant p53 upregulates endosomal recycling of EGFR and integrins by interacting with p63.
  • Inhibition of endosomal trafficking enhances EGFR signaling potency.
  • Cancer cells exhibit increased proinvasive abilities due to EGFR and integrin upregulation.

Conclusions:

  • The limited efficacy of anti-EGFR therapies in TNBC may be due to enhanced EGFR signaling via increased endosomal recycling.
  • Mutant p53 plays a critical role in this process by affecting p63 function and promoting endosomal trafficking.
  • Combining endosomal trafficking inhibitors with anti-EGFR treatments holds promise for improving clinical outcomes in TNBC.
Keywords:
Basal like breast cancerEGFREndosomal traffickingIntegrinTriple negative breast cancerp53 mutationp63

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