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Article

Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation

by 1,†, 2,3,4,5,†, 6,†, 7, 8,9,10, 1,11, 12,13, 14,15,* and 1,6,7,16,17,18,*
1
Graduate Institute of Biomedical Science, China Medical University, Taichung 404, Taiwan
2
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan
3
Department of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan
4
Physical Examination Center, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan
5
Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan
6
Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan
7
Department of Biotechnology, Asia University, Taichung 413, Taiwan
8
Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan
9
School of Medicine for International Students, I-Shou University, Kaohsiung 824, Taiwan
10
Department of Pharmacy, E-Da Hospital, Kaohsiung 824, Taiwan
11
Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung 404, Taiwan
12
School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan
13
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan
14
Department of Plastic Surgery, Show Chwan Memorial Hospital, Changhua 500, Taiwan
15
Innovation Research Center, Show Chwan Health Care System, Changhua 500, Taiwan
16
The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan
17
Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan
18
Drug Development Center, China Medical University, Taichung 404, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4812; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194812
Received: 14 August 2019 / Revised: 19 September 2019 / Accepted: 21 September 2019 / Published: 27 September 2019
(This article belongs to the Special Issue Multikinase Inhibitors and Cancer)
Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors. View Full-Text
Keywords: breast cancer; ErbB family; proteasome; lysosome; and HSP90 breast cancer; ErbB family; proteasome; lysosome; and HSP90
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MDPI and ACS Style

Huynh, T.K.; Ho, C.-Y.; Tsai, C.-H.; Wang, C.-K.; Chen, Y.-J.; Bau, D.-T.; Tu, C.-Y.; Li, T.-S.; Huang, W.-C. Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation. Int. J. Mol. Sci. 2019, 20, 4812. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194812

AMA Style

Huynh TK, Ho C-Y, Tsai C-H, Wang C-K, Chen Y-J, Bau D-T, Tu C-Y, Li T-S, Huang W-C. Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation. International Journal of Molecular Sciences. 2019; 20(19):4812. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194812

Chicago/Turabian Style

Huynh, Thanh K., Chien-Yi Ho, Chi-Hua Tsai, Chien-Kuo Wang, Yun-Ju Chen, Da-Tian Bau, Chih-Yen Tu, Tzong-Shiun Li, and Wei-Chien Huang. 2019. "Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation" International Journal of Molecular Sciences 20, no. 19: 4812. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194812

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