دورية أكاديمية
BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer
| العنوان: | BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer |
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| المؤلفون: | Pandya, Vrajesh, Githaka, John Maringa, Patel, Namrata, Veldhoen, Richard, Hugh, Judith, Damaraju, Sambasivarao, McMullen, Todd, Mackey, John, Goping, Ing Swie |
| المساهمون: | Alberta Cancer Foundation, Canadian Breast Cancer Foundation |
| المصدر: | Cell Death & Disease ; volume 11, issue 6 ; ISSN 2041-4889 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Cell Biology, Cellular and Molecular Neuroscience, Immunology |
| الوصف: | Apoptosis is fundamental to normal animal development and is the target for many anticancer therapies. Recent studies have explored the consequences of “failed apoptosis” where the apoptotic program is initiated but does not go to completion and does not cause cell death. Nevertheless, this failed apoptosis induces DNA double-strand breaks generating mutations that facilitate tumorigenesis. Whether failed apoptosis is relevant to clinical disease is unknown. BCL-2 interacting killer (BIK) is a stress-induced BH3-only protein that stimulates apoptosis in response to hormone and growth factor deprivation, hypoxia, and genomic stress. It was unclear whether BIK promotes or suppresses tumor survival within the context of breast cancer. We investigated this and show that BIK induces failed apoptosis with limited caspase activation and genomic damage in the absence of extensive cell death. Surviving cells acquire aggressive phenotypes characterized by enrichment of cancer stem-like cells, increased motility and increased clonogenic survival. Furthermore, by examining six independent cohorts of patients (total n = 969), we discovered that high BIK mRNA and protein levels predicted clinical relapse of Estrogen receptor (ER)-positive cancers, which account for almost 70% of all breast cancers diagnosed but had no predictive value for hormone receptor-negative (triple-negative) patients. Thus, this study identifies BIK as a biomarker for tumor recurrence of ER-positive patients and provides a potential mechanism whereby failed apoptosis contributes to cancer aggression. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41419-020-2654-2 |
| الإتاحة: | https://doi.org/10.1038/s41419-020-2654-2Test https://www.nature.com/articles/s41419-020-2654-2.pdfTest https://www.nature.com/articles/s41419-020-2654-2Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.A711E782 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41419-020-2654-2 |
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