Dataset Information

C-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6779757 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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c-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment.

Liu Yiming Y Zhou Sining S Shi Jieyao J Zhang Xiaodi X Shentu Linhui L Chen Zhi Z Zhou Linfu L

Oncogenesis 20191007 10

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 tha ...[more]

PMID: 31591387

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Project description:Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC. Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score. Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts. Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

Dataset Information

C-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment.

Publications

c-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment.

Similar Datasets

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