Open Access
Open access
Oxidative Medicine and Cellular Longevity, volume 2017, pages 1-19

NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib

Publication typeJournal Article
Publication date2017-02-27
Quartile SCImago
Q1
Quartile WOS
Impact factor
ISSN19420900, 19420994
PubMed ID:  29410730
Biochemistry
General Medicine
Cell Biology
Aging
Abstract
NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy.

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GOST Copy
Kankia I. H. et al. NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib // Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017. pp. 1-19.
GOST all authors (up to 50) Copy
Kankia I. H., Khalil H. S., Langdon S., Moult P., Bown J. L., Deeni Y. Y. NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib // Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017. pp. 1-19.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1155/2017/1864578
UR - https://doi.org/10.1155%2F2017%2F1864578
TI - NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib
T2 - Oxidative Medicine and Cellular Longevity
AU - Kankia, Ibrahim H
AU - Khalil, Hilal S
AU - Langdon, Simon P.
AU - Moult, Peter R.
AU - Bown, James L
AU - Deeni, Yusuf Y.
PY - 2017
DA - 2017/02/27 00:00:00
PB - Hindawi Limited
SP - 1-19
VL - 2017
PMID - 29410730
SN - 1942-0900
SN - 1942-0994
ER -
BibTex
Cite this
BibTex Copy
@article{2017_Kankia
author = {Ibrahim H Kankia and Hilal S Khalil and Simon P. Langdon and Peter R. Moult and James L Bown and Yusuf Y. Deeni},
title = {NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib},
journal = {Oxidative Medicine and Cellular Longevity},
year = {2017},
volume = {2017},
publisher = {Hindawi Limited},
month = {feb},
url = {https://doi.org/10.1155%2F2017%2F1864578},
pages = {1--19},
doi = {10.1155/2017/1864578}
}
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