Liu Yiming, Zhou Sining, Shi Jieyao, Zhang Xiaodi, Shentu Linhui, Chen Zhi, Zhou Linfu
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Oncogenesis. 2019 Oct 7;8(10):58. doi: 10.1038/s41389-019-0166-7.
Golgi phosphoprotein 73 (GP73), encoded by GOLM1, is a highly expressed factor in hepatocellular carcinoma (HCC) cells and has been regarded for several years as a remarkable serum biomarker for the diagnosis of HCC. Recently, it was found that upregulation of GP73 promotes cancer metastasis, but the mechanism is complex, and it is even unclear how the gene is transactivated in HCC cells. In this study, it was discovered that c-Myc transactivated GP73 in a mildly hypoxic microenvironment and that the activation of c-Myc upregulated the expression of matrix metalloproteinase-7 (MMP-7). Moreover, it is shown that GP73 interacted with intracellular MMP-7 in the region of the cytoplasmic domain and facilitated the trafficking and secretion of MMP-7, resulting in cell metastasis. This study indicates that GP73 is transactivated by c-Myc and serves as a transporter in the trafficking of intracellular MMP-7 in HCC cells. These findings suggest that GP73 is a potential target for combating metastatic HCC.
高尔基体磷蛋白73（GP73）由GOLM1编码，是一种在肝癌（HCC）细胞中高表达的因子，多年来一直被视为诊断肝癌的重要血清生物标志物。最近发现，GP73的上调促进癌症转移，但其机制复杂，甚至不清楚该基因在肝癌细胞中是如何被反式激活的。在本研究中，发现c-Myc在轻度缺氧微环境中反式激活GP73，且c-Myc的激活上调了基质金属蛋白酶-7（MMP-7）的表达。此外，研究表明GP73在细胞质结构域区域与细胞内MMP-7相互作用，并促进MMP-7的运输和分泌，从而导致细胞转移。本研究表明，GP73被c-Myc反式激活，并在肝癌细胞中细胞内MMP-7的运输中充当转运体。这些发现表明，GP73是对抗转移性肝癌的潜在靶点。
