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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.9K

A mutant p53/Hif1α/miR-30d axis reprograms the secretory pathway promoting the release of a prometastatic secretome

Valeria Capaci1,2, Fiamma Mantovani1, Giannino Del Sal1,2,3

  • 1Dipartimento di Scienze della Vita, Università degli Studi di Trieste - Trieste (TS), 34127 - Italy.

Cell Stress
|November 5, 2020
PubMed

Insights

Mutant TP53 (mut-p53) proteins promote cancer by altering gene expression and Golgi apparatus function. This leads to a secretome that enhances tumor growth and metastasis, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • TP53 missense mutations are common in cancer, producing mutant p53 (mut-p53) with oncogenic functions.
  • Mut-p53 loses tumor suppressive activity and gains pro-tumorigenic features, impacting growth, metastasis, and chemoresistance.
  • Mut-p53 alters cellular pathways, notably gene expression, contributing to cancer progression.

Purpose of the Study:

  • To investigate the mechanisms by which mut-p53 influences tumor progression.
  • To elucidate the role of mut-p53 in altering cellular functions and the tumor microenvironment.
  • To identify potential therapeutic targets and biomarkers for mut-p53-driven cancers.

Main Methods:

  • Analysis of TP53 mutations and their impact on p53 protein function.
  • Investigated the role of miR-30d in mut-p53-mediated Golgi apparatus modification and trafficking.
  • Utilized cell-based assays and mouse xenograft models to assess the impact on the tumor microenvironment and metastasis.

Main Results:

  • Mut-p53, via miR-30d, alters Golgi apparatus structure and function, increasing cellular trafficking rates.
  • This leads to the release of a pro-malignant secretome that remodels the tumor microenvironment.
  • The secretome increases extracellular matrix stiffness, promoting metastatic colonization.

Conclusions:

  • Mut-p53 induces pro-tumorigenic functions through non-coding RNAs in a non-cell-autonomous manner.
  • The study highlights the Golgi apparatus and secretome as key mediators of mut-p53 oncogenicity.
  • Identified potential non-invasive biomarkers and therapeutic strategies for mut-p53-harboring tumors.
Keywords:
Golgi ApparatusmiR-30dmicroenvironmentmutant p53secretory machinery

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