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NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib
Joint Authors
Khalil, Hilal S.
Langdon, Simon P.
Kankia, Ibrahim H.
Bown, James
Deeni, Yusuf Y.
Moult, Peter R.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-19, 19 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-12-19
Country of Publication
Egypt
No. of Pages
19
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Kankia, Ibrahim H.& Khalil, Hilal S.& Langdon, Simon P.& Moult, Peter R.& Bown, James& Deeni, Yusuf Y.. 2017. NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-19.
https://search.emarefa.net/detail/BIM-1193956
Modern Language Association (MLA)
Kankia, Ibrahim 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 No. 2017 (2017), pp.1-19.
https://search.emarefa.net/detail/BIM-1193956
American Medical Association (AMA)
Kankia, Ibrahim H.& Khalil, Hilal S.& Langdon, Simon P.& Moult, Peter R.& Bown, James& Deeni, Yusuf 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, no. 2017, pp.1-19.
https://search.emarefa.net/detail/BIM-1193956
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193956