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Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors
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Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors

Published on: March 1, 2020

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Activation of NRF2 by p62 and proteasome reduction in sphere-forming breast carcinoma cells

In-Geun Ryoo1, Bo-Hyun Choi1, Mi-Kyoung Kwak1

  • 1College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do, Republic of Korea.

Oncotarget
|February 27, 2015
PubMed

Insights

Cancer stem cells (CSCs) resist treatment partly due to high antioxidant gene activity. This study shows Nuclear factor erythroid 2-related factor 2 (NRF2) activation in CSCs drives this resistance and survival.

Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Stem Cell Research

Background:

  • Cancer stem cells (CSCs) are implicated in tumor recurrence post-therapy.
  • CSCs exhibit high drug efflux and antioxidant gene expression.
  • NRF2 (Nuclear factor erythroid 2-related factor 2) is a key regulator of antioxidant genes.

Purpose of the Study:

  • To investigate the role of NRF2 in the survival and stress resistance of CSC-enriched mammospheres.
  • To elucidate the mechanisms underlying NRF2 activation in CSCs.

Main Methods:

  • Comparison of NRF2 protein and target gene expression in MCF7 mammospheres versus monolayer cultures.
  • Analysis of proteasome activity and p62 expression in mammospheres.
  • Functional assessment of NRF2 by knockdown experiments in mammospheres.
  • Confirmation of NRF2 upregulation in colon and ovarian cancer sphere cultures.

Main Results:

  • MCF7 mammospheres showed significantly higher NRF2 protein and target gene expression than monolayer cultures.
  • Mammospheres exhibited decreased proteasome activity and altered p62 expression, correlating with NRF2 activation.
  • NRF2 knockdown in mammospheres led to increased cell death, reduced sphere growth, and loss of anticancer drug resistance.

Conclusions:

  • Altered proteasome function and p62 expression contribute to NRF2 activation in CSC-enriched mammospheres.
  • NRF2 plays a critical role in CSC survival and the development of anticancer drug resistance.
  • Targeting NRF2 may represent a therapeutic strategy to overcome CSC-mediated treatment failure.
Keywords:
NRF2cancer stem cellmammospheresp62resistance

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