Related Experiment Video

Updated: Nov 3, 2025

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

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Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and

Ann-Kathrin Eichelmann1,2, George C Mayne1,3, Karen Chiam1

  • 1Flinders Health and Medical Research Institute-Cancer Program, Flinders University, Bedford Park, Adelaide, SA 5042, Australia.

International Journal of Molecular Sciences
|June 2, 2021
PubMed

Insights

Mutant TP53 gene in esophageal adenocarcinoma promotes resistance to chemotherapy and radiation. Inhibiting SLC7A11 may overcome this resistance, offering new therapeutic strategies for OAC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • TP53 gene mutations are prevalent in esophageal adenocarcinoma (OAC).
  • Mutant p53 influences cellular response to cancer therapies.
  • SLC7A11's role in cancer metabolism and redox balance is under investigation.

Purpose of the Study:

  • To investigate the role of mutant p53 and SLC7A11 in OAC treatment resistance.
  • To analyze the impact of TP53 knockout on cellular response to various therapies.
  • To identify miRNA expression changes and related pathways in OAC models.

Main Methods:

  • CRISPR-mediated TP53 knockout in JH-EsoAd1 OAC cell line.
  • Assessment of cellular response to irradiation and chemotherapies (cisplatin, 5-FU).
  • TaqMan OpenArray qPCR for miRNA expression profiling and pathway analysis.

Main Results:

  • TP53 knockout increased resistance to chemo- and radiotherapy.
  • miRNA expression levels were altered post-knockout.
  • SLC7A11 knockdown restored radiosensitivity, potentially via enhanced oxidative stress sensitivity.

Conclusions:

  • Mutant p53, even if non-functional, contributes to radio- and chemoresistance in OAC.
  • SLC7A11 plays a significant role in cancer metabolism and redox balance, influenced by p53.
  • Targeting the SLC7A11-glutathione axis is a promising strategy to overcome mut-p53-associated resistance.
Keywords:
SLC7A11chemoresistancemiR-27a-3pmiRNAoesophageal canceroestrogen receptor modulatorradioresistancereactive oxidative speciesribosomexCT

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