MZF-1/Elk-1/PKCα is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

Je-Chiuan Ye; Li-Sung Hsu; Jen-Hsiang Tsai; Hsin-Ling Yang; Meen-Woon Hsiao; Jin-Ming Hwang; Chia-Jen Lee; Jer-Yuh Liu

doi:10.7150/jca.20467

MZF-1/Elk-1/PKCα is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

J Cancer. 2017 Sep 2;8(15):3028-3036. doi: 10.7150/jca.20467. eCollection 2017.

Authors

Je-Chiuan Ye¹, Li-Sung Hsu^{2

3}, Jen-Hsiang Tsai⁴, Hsin-Ling Yang⁵, Meen-Woon Hsiao⁶, Jin-Ming Hwang⁶, Chia-Jen Lee⁷, Jer-Yuh Liu^{8

9}

Affiliations

¹ Bachelor Program of Senior Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
² Institute of Biochemistry and Biotechnology, Medical College, Chung-Shan Medical University, Taichung, Taiwan.
³ Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁴ Department Physical Therapy, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan.
⁵ Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
⁶ Department of Medical Applied Chemistry, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan.
⁷ Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
⁸ Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
⁹ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.

Abstract

Background: Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. Methods: By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. Results: The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-1_60-72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. Conclusion: These findings could be used to develop an alternative therapeutic strategy against patients with the PKCα-derived HCC.

Keywords: Elk-1; HCC.; MZF-1; PKCα.