Non-canonical p53 signaling to promote invasion

Paul Dent1

  • 1Department of Neurosurgery; Massey Cancer Center; Virginia Commonwealth University; Richmond, VA USA.

Cancer Biology & Therapy
|September 13, 2013
PubMed

Insights

Mutated p53 proteins gain oncogenic functions, promoting cell transformation and invasion. These studies reveal increased c-Met activity as the mechanism driving invasiveness in transformed esophageal cells.

Area of Science:

  • Molecular Biology
  • Cancer Research

Background:

  • Mutated p53 proteins can acquire oncogenic functions, distinct from loss of normal p53 activity.
  • Expression of mutant p53 (R175H) and ERBB1 transforms esophageal cells, increasing migration.

Purpose of the Study:

  • To elucidate the mechanism by which p53-mutated esophageal cells become invasive.
  • To investigate the role of c-Met activity in cell invasion.

Main Methods:

  • Cell transformation assays.
  • Analysis of gene expression and protein activity.
  • Assessment of cell migratory and invasive capabilities.

Main Results:

  • Transduction of p53-null cells with mutant p53 can induce cell transformation.
  • Increased c-Met activity was identified as the key factor responsible for the invasiveness of transformed esophageal cells.

Conclusions:

  • Mutant p53 confers oncogenic functions, leading to cell transformation and invasion.
  • Elevated c-Met activity is a critical mediator of invasiveness in esophageal cells expressing mutant p53.

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