Abstract
The systematic investigation of gene mutation and expression is important to discover novel biomarkers and therapeutic targets in cancers. Here, we integrated genomics, transcriptomics, proteomics, and metabolomics to analyze three hepatocellular carcinoma (HCC) cell lines with differential metastatic potentials. The results revealed the profile of the prometastasis metabolism potentially associated with HCC metastasis. The multiomic analysis identified 12 genes with variations at multiple levels from three metabolic pathways, including glycolysis, starch, and sucrose metabolism, and glutathione metabolism. Furthermore, uridine diphosphate (UDP)-glucose pyrophosphorylase 2 (UGP2), was observed to be persistently up-regulated with increased metastatic potential. UGP2 overexpression promoted cell migration and invasion and enhanced glycogenesis in vitro The role of UGP2 in metastasis was further confirmed using a tumor xenograft mouse model. Taken together, the compendium of multiomic data provides valuable insights in understanding the roles of shifted cellular metabolism in HCC metastasis.
Highlights
Hepatocellular carcinoma (HCC)1 is the second leading cause of cancer-related death in the world [1]
Higher levels of glycogen were detected in the tumors from mice injected with UDP-glucose pyrophosphorylase 2 (UGP2)-overexpressing cells as compared with the mice injected with the corresponding control cells (Fig. 6H). These results indicate that higher level of glycogen could be beneficial for HCC tumor cells to survive the nutrient-deprived condition during metastasis, and UGP2 may play an important role in cell migration and metastasis through the regulation of glycogen synthesis in HCC
The integrative multiomic analysis of three HCC cell lines with different metastatic potentials revealed the link between metabolism and metastasis
Summary
Hepatocellular carcinoma (HCC)1 is the second leading cause of cancer-related death in the world [1]. We integrated data of genomics, transcriptomics, proteomics, and metabolomics from three HCC cell lines, including a low-metastatic cell line, Huh7; a medium-metastatic cell line, MHCC97L; and a highly metastatic cell line, HCCLM3, to mine potential genes and pathways contributing to HCC metastasis.
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