NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies
Joint Authors
Khalil, Hilal S.
Langdon, Simon P.
Kankia, Ibrahim H.
Bown, James
Deeni, Yusuf Y.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-22, 22 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-12-07
Country of Publication
Egypt
No. of Pages
22
Main Subjects
Abstract EN
NF-E2 related factor-2 (NRF2) is an essential transcription factor for multiple genes encoding antioxidants and detoxification enzymes.
NRF2 is implicated in promoting cancer therapeutic resistance by its detoxification function and crosstalk with proproliferative pathways.
However, the exact mechanism of this intricate connectivity between NRF2 and growth factor induced proliferative pathway remains elusive.
Here, we have demonstrated that pharmacological activation of NRF2 by tert-butylhydroquinone (tBHQ) upregulates the HER family receptors, HER2 and HER3 expression, elevates pAKT levels, and enhances the proliferation of ovarian cancer cells.
Preactivation of NRF2 also attenuates the combined growth inhibitory effects of HER2 targeting monoclonal antibodies, Pertuzumab and Trastuzumab.
Further, tBHQ caused transcriptional induction of HER2 and HER3, while SiRNA-mediated knockdown of NRF2 prevented this and further caused transcriptional repression and enhanced cytotoxicity of the HER2 inhibitors.
Hence, NRF2 regulates both HER2 and HER3 receptors to influence cellular responses to HER2 targeting monoclonal antibodies.
This deciphered crosstalk mechanism reinforces the role of NRF2 in drug resistance and as a relevant anticancer target.
American Psychological Association (APA)
Khalil, Hilal S.& Langdon, Simon P.& Kankia, Ibrahim H.& Bown, James& Deeni, Yusuf Y.. 2015. NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-22.
https://search.emarefa.net/detail/BIM-1113905
Modern Language Association (MLA)
Khalil, Hilal S.…[et al.]. NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-22.
https://search.emarefa.net/detail/BIM-1113905
American Medical Association (AMA)
Khalil, Hilal S.& Langdon, Simon P.& Kankia, Ibrahim H.& Bown, James& Deeni, Yusuf Y.. NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies. Oxidative Medicine and Cellular Longevity. 2015. Vol. 2016, no. 2016, pp.1-22.
https://search.emarefa.net/detail/BIM-1113905
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1113905