Related Experiment Video

Updated: Jan 6, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
12:09

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

Published on: December 30, 2025

13

Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate

Asja Guzman1, Tatsuya Kawase2, Alexander J Devanny3

  • 1Department of Biological Sciences, Columbia University, New York, NY 10027.

Proceedings of the National Academy of Sciences of the United States of America
|October 21, 2025
PubMed

Insights

Mutant TP53 protein enhances cancer cell invasion by boosting cell contractility and extracellular matrix remodeling. This gain of function is linked to metabolic pathways and influenced by the tumor microenvironment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Certain TP53 mutations confer neomorphic gain of function (GOF) activities to p53, impacting cancer progression.
  • The concept of mutant p53 GOF has faced scrutiny, necessitating further investigation.

Purpose of the Study:

  • To demonstrate that mutant p53 stimulates cancer cell invasion.
  • To elucidate the mechanisms underlying mutant p53-mediated invasion.
  • To explore the role of cell-ECM interactions in regulating mutant p53 GOF activity.

Main Methods:

  • Utilized various strategies to alter mutant p53 status in cell lines.
  • Assessed cancer cell invasion in three-dimensional environments.
  • Investigated RhoA/ROCK signaling, mevalonate pathway, and cell-ECM interactions.

Main Results:

  • Mutant p53 was shown to stimulate cancer cell invasion in 3D.
  • Mutant p53 enhances RhoA/ROCK-dependent cell contractility and ECM reorganization.
  • Mevalonate pathway activity, specifically IDI-1, mediates RhoA-dependent proinvasive effects.
  • Mutant p53's invasion-enhancing effect is modulated by ECM biomechanical properties and cell-ECM interactions.

Conclusions:

  • Mutant p53's metabolic GOF activity is linked to a context-dependent invasive cellular phenotype.
  • Findings highlight a cell-independent regulatory layer involving dynamic cell-ECM interactions.
  • This study provides mechanistic insights into mutant p53 GOF and its role in cancer progression.
Keywords:
IDI-1Rho/ROCK signalinginvasionmevalonate pathwaymutant p53

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