Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation
| العنوان: | Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation |
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| المؤلفون: | Hui Lin Wang, Yu Hao Huang, Huei Fan Yang, Wen-Wei Chang, Hsin Lin Chen, Ying Hsiang Chou, Hsueh Te Lee, Bing Yen Wang, Hsien Chun Tseng, Guan Ci Hong, Chun-Chieh Wu, Shao Ti Li, Wen Ling Wang, Yueh-Chun Lee, Wei Chao Chang |
| المصدر: | Cancers, Vol 11, Iss 2, p 127 (2019) Cancers Volume 11 Issue 2 |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.medical_treatment, Population, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cancer stem cell, Radioresistance, medicine, education, Triple-negative breast cancer, Notch1, education.field_of_study, business.industry, TRIB3, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, radioresistance, Radiation therapy, 030104 developmental biology, Oncology, triple negative breast cancer, 030220 oncology & carcinogenesis, Cancer research, business |
| الوصف: | Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4ab436e0c61a8ce2d1af2ae908a7cb8 https://doi.org/10.3390/cancers11020127 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a4ab436e0c61a8ce2d1af2ae908a7cb8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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