MZF-1/Elk-1 interaction domain as therapeutic target for protein kinase Cα-based triple-negative breast cancer cells
Metrics: PDF 717 views | HTML 1446 views | ?
Chia-Jen Lee1, Li-Sung Hsu2,3, Chia-Herng Yue4,5, Ho Lin5, Yung-Wei Chiu6, Yu-Yu Lin7, Chih-Yang Huang8,9,10, Mien-Chie Hung1,7,11, Jer-Yuh Liu1,7
1Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan
2Institute of Biochemistry, Microbiology and Immunology, Medical College, Chung-Shan Medical University, Taichung 40201, Taiwan
3Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
4Department of Surgery, Tungs’ Taichung Metro Harbor Hospital, Taichung 435, Taiwan
5Department of Life Science, National Chung Hsing University, Taichung 402, Taiwan
6Emergency Department and Center of Hyperbaric Oxygen Therapy, Tungs’ Taichung Metro Harbor Hospital, Taichung 435, Taiwan
7Graduate Institute of Cancer Biology, China Medical University, Taichung 40402, Taiwan
8Graduate Institute of Chinese Medical Science, School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
9Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan
10Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
11Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
Jer-Yuh Liu, email: email@example.com
Mien-Chie Hung, email: firstname.lastname@example.org
Chih-Yang Huang, email: email@example.com
Keywords: MZF-1, Elk-1, PKCα, triple-negative breast cancer cells
Received: December 09, 2015 Accepted: July 06, 2016 Published: August 17, 2016
Recent reports demonstrate that the expression of protein kinase C alpha (PKCα) in triple-negative breast cancer (TNBC) correlates with decreased survival outcomes. However, off-target effects of targeting PKCα and limited understanding of the signaling mechanisms upstream of PKCα have hampered previous efforts to manipulate this ubiquitous gene. This study shows that the expression of both myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) correlates with PKCα expression in TNBC. We found that the acidic domain of MZF-1 and the heparin-binding domain of Elk-1 facilitate the heterodimeric interaction between the two genes before the complex formation binds to the PKCα promoter. Blocking the formation of the heterodimer by transfection of MZF-160–72 or Elk-1145–157 peptide fragments at the MZF-1 / Elk-1 interface decreases DNA-binding activity of the MZF-1 / Elk-1 complex at the PKCα promoter. Subsequently, PKCα expression, migration, tumorigenicity, and the epithelial–mesenchymal transition potential of TNBC cells decrease. These subsequent effects are reversed by transfection with full-length PKCα, confirming that the MZF-1/Elk-1 heterodimer is a mediator of PKCα in TNBC cells. These data suggest that the next therapeutic strategy in treating PKCα-related cancer will be developed from blocking MZF-1/Elk-1 interaction through their binding domain.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.