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Author Notes:

Correspondence should be addressed to Keqiang Ye; kye@emory.edu

We are indebted to Dr. Arthur W. English at Emory University for critical proofreading the manuscript.

The authors are thankful for Dr. Wolfdieter Springer in Mayo Clinics, Jacksonville, FL, for the constructs of His-PINK1 and Flag-Parkin.

The authors are thankful for Dr. Paul S. Mischel, Department of Pathology, UCSD School of Medicine, La Jolla, CA 92093, USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093, USA, for the U87MG stable cell lines.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This work is funded in part with Federal funds from National Cancer Institute (NCI), National Institutes of Health (NIH) NIH grant RO1 CA186918 (K.Y.), and National Natural Science Foundation of China (No. 81503358 and No. 81672781).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • GROWTH-FACTOR RECEPTOR
  • TUMOR-SUPPRESSOR PTEN
  • NAD(P)H-QUINONE OXIDOREDUCTASE
  • PARKINSONS-DISEASE
  • LUNG-CANCER
  • SIGNALING PATHWAY
  • HYDROGEN-PEROXIDE
  • PINK1
  • GENE
  • MUTATIONS

NQO1 Is Regulated by PTEN in Glioblastoma, Mediating Cell Proliferation and Oxidative Stress

Tools:

Journal Title:

Oxidative Medicine and Cellular Longevity

Volume:

Volume 2018

Publisher:

, Pages 9146528-9146528

Type of Work:

Article | Final Publisher PDF

Abstract:

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a dismal prognosis, and the patients carrying EGFR-driven tumors with PTEN mutation do not respond to anti-EGFR therapy. The molecular mechanisms for this resistance remain unknown. Here, we show that PTEN induces the expression of NQO1, a flavoenzyme with dual roles in pro- and antitumorigenesis that decreases the formation of reactive oxygen species (ROS), which mediates the oxidative stress and GBM cell proliferation. NQO1 is reduced in EGFRvIII-overexpressed U87MG cells associated with low ROS, whereas NQO1 is highly escalated in PTEN stably expressed U87MG/EGFRvIII cells with high ROS. Interestingly, knockdown of NQO1 augments ROS and diminishes cell proliferation. Conversely, overexpression of NQO1 attenuates ROS and increases cell proliferation. By contrast, overexpression of PINK1, a PTEN-induced kinase 1, represses ROS and inhibits GBM cell proliferation. Therefore, our findings support that NQO1 displays a paradoxical role in mediating GBM growth in response to tumor suppressor PTEN.

Copyright information:

© 2018 Shilin Luo et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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