Full text

Turn on search term navigation

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation
Author
Yueh-Chun, Lee 1 ; Wen-Ling, Wang 2 ; Wei-Chao, Chang 3 ; Yu-Hao, Huang 2 ; Guan-Ci Hong 2 ; Hui-Lin, Wang 2 ; Ying-Hsiang Chou 4   VIAFID ORCID Logo  ; Hsien-Chun Tseng 5 ; Hsueh-Te, Lee 6   VIAFID ORCID Logo  ; Shao-Ti, Li 1 ; Hsin-Lin, Chen 1 ; Wu, Chun-Chieh 1 ; Huei-Fan Yang 7 ; Bing-Yen, Wang 8 ; Wen-Wei, Chang 9   VIAFID ORCID Logo 

 Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan 
 School of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan 
 Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 40402, Taiwan 
 Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan; Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, Taiwan 
 Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan 
 Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei 11221, Taiwan 
 Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan; Department of Nursing, Chung shan Medical University Hospital, Taichung 40201, Taiwan 
 Division of Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Changhua City 50006, Taiwan; Center for General Education, Ming Dao University, Changhua 52345, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40201, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40201, Taiwan 
 School of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan 
First page
127
Publication year
2019
Publication date
2019
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2547490773
Copyright
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.