NCOA3 coactivator is a transcriptional target of XBP1 and regulates PERK–eIF2α–ATF4 signalling in breast cancer
| العنوان: | NCOA3 coactivator is a transcriptional target of XBP1 and regulates PERK–eIF2α–ATF4 signalling in breast cancer |
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| المؤلفون: | Grace Callagy, Nicola Miller, Ananya Gupta, Sanjeev Gupta, Michael J. Kerin, Muhammad Mosaraf Hossain |
| المصدر: | Oncogene |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | X-Box Binding Protein 1, 0301 basic medicine, endoplasmic-reticulum stress, Cancer Research, XBP1, Transcription, Genetic, Eukaryotic Initiation Factor-2, Breast Neoplasms, er stress, Protein Serine-Threonine Kinases, Biology, Nuclear Receptor Coactivator 3, eIF-2 Kinase, 03 medical and health sciences, Breast cancer, cell fate decisions, Cell Line, Tumor, expression, Endoribonucleases, Coactivator, Genetics, medicine, Humans, RNA, Messenger, Molecular Biology, Transcription factor, ATF4, Cancer, Endoplasmic Reticulum Stress, Prognosis, medicine.disease, Activating Transcription Factor 4, translational regulation, Gene Expression Regulation, Neoplastic, perk, 030104 developmental biology, messenger-rna, Nuclear receptor coactivator 3, Unfolded Protein Response, Cancer research, Unfolded protein response, activation, Female, Original Article, steroid-receptor coactivator-3, Signal Transduction |
| الوصف: | XBP1 is a multitasking transcription factor and a key component of the unfolded protein response (UPR). Despite the wealth of knowledge about the role of XBP1 in luminal/ER-positive breast cancer, not much is known about the effectors of XBP1 in this context. Here we show that NCOA3 is a transcriptional target of XBP1. We observed increased expression of NCOA3 during conditions of UPR and oestrogen (E2) stimulation. Further investigations revealed a role for the IRE1-XBP1 axis in the induction of NCOA3 during UPR and oestrogen signalling. We identify a novel role for NCOA3 in activation of PERK-ATF4 axis during UPR where knockdown of NCOA3 compromised the optimal activation of the PERK-ATF4 pathway. We found that NCOA3 is required for induction of XBP1 during E2 stimulation and uncover a positive feedback regulatory loop that maintains high levels of NCOA3 and XBP1 in breast cancer. Furthermore, upregulated NCOA3 was required for XBP1-mediated resistance to antihormonal agents. Increased expression of NCOA3 was associated with poor prognosis and higher levels of XBP1-S in breast cancer tissues. Our results uncover a novel steroid hormone-independent role for NCOA3 in UPR signalling. Further we identify a positive feedback regulatory loop consisting of XBP1 and NCOA3 that maintains high levels of NCOA3 and XBP1 expression in breast cancer tissues. Taken together our data identify XBP1-NCOA3 axis that regulates cell fate decisions in ER-positive breast cancer cells. |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2973a407bdcecdc937330220641d87dd https://doi.org/10.1038/onc.2016.121 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2973a407bdcecdc937330220641d87dd |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765594 09509232 |
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