Ye Je-Chiuan, Hsu Li-Sung, Tsai Jen-Hsiang, Yang Hsin-Ling, Hsiao Meen-Woon, Hwang Jin-Ming, Lee Chia-Jen, Liu Jer-Yuh
Bachelor Program of Senior Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
Institute of Biochemistry and Biotechnology, Medical College, Chung-Shan Medical University, Taichung, Taiwan.
J Cancer. 2017 Sep 2;8(15):3028-3036. doi: 10.7150/jca.20467. eCollection 2017.
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. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. 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 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy against patients with the PKCα-derived HCC.
蛋白激酶Cα（PKCα）是人类癌症发展中的关键信号分子。作为一种治疗策略，靶向PKCα具有挑战性，因为该分子在非恶性细胞中广泛表达。在人类癌细胞中，PKCα受转录因子髓样锌指1（MZF-1）和Ets样蛋白1（Elk-1）的协同相互作用调控。在此，我们通过组织芯片分析确定了MZF-1/Elk-1/PKCα在各种癌症中的蛋白表达。数据显示，MZF-1/Elk-1的表达与肝细胞癌（HCC）中的PKCα表达相关，但在膀胱癌和肺癌中不相关。此外，仅在HCC SK-Hep-1细胞中观察到通过shRNA Elk-1使PKCα下调。通过转染其结合域MZF-1来阻断MZF-1与Elk-1之间的相互作用会降低PKCα表达。这一步最终降低了HCC细胞的上皮-间质转化潜能。这些发现可用于开发针对PKCα相关HCC患者的替代治疗策略。
