Targeting UDP-glucose dehydrogenase inhibits ovarian cancer growth and metastasis.

Abstract

More than 70% of patients with ovarian cancer are diagnosed in advanced stages. Therefore, it is urgent to identify a promising prognostic marker and understand the mechanism of ovarian cancer metastasis development. By using proteomics approaches, we found that UDP-glucose dehydrogenase (UGDH) was up-regulated in highly metastatic ovarian cancer TOV21G cells, characterized by high invasiveness (TOV21GHI ), in comparison to its parental control. Previous reports demonstrated that UGDH is involved in cell migration, but its specific role in cancer metastasis remains unclear. By performing immunohistochemical staining with tissue microarray, we found overexpression of UGDH in ovarian cancer tissue, but not in normal adjacent tissue. Silencing using RNA interference (RNAi) was utilized to knockdown UGDH, which resulted in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH caused cell cycle arrest in the G0 /G1 phase and induced a massive decrease of tumour formation rate in vivo. Our data showed that UGDH-depletion led to the down-regulation of epithelial-mesenchymal transition (EMT)-related markers as well as MMP2, and inactivation of the ERK/MAPK pathway. In conclusion, we found that the up-regulation of UGDH is related to ovarian cancer metastasis and the deficiency of UGDH leads to the decrease of cell migration, cell invasion, wound healing and cell proliferation ability. Our findings reveal that UGDH can serve as a prognostic marker and that the inhibition of UGDH is a promising strategy for ovarian cancer treatment.

• Authors: Li-Hsun Lin, Hsiu-Chuan Chou, Shing-Jyh Chang, En-Chi Liao, Yi-Ting Tsai, Yu-Shan Wei, Hsin-Yi Chen, Meng-Wei Lin, Yi-Shiuan Wang, Yu-An Chien, Xin-Ru Yu, Hong-Lin Chan
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 20 Pg. 11883-11902 (10 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32893977 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Actins
• RNA, Small Interfering
• Uridine Diphosphate Glucose Dehydrogenase

Topics

• Actins (metabolism)
• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Female
• G1 Phase Cell Cycle Checkpoints
• Gene Knockdown Techniques
• Humans
• MAP Kinase Signaling System
• Mice, Inbred BALB C
• Mice, Nude
• Models, Biological
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Ovarian Neoplasms (enzymology, pathology)
• Polymerization
• Proteomics
• RNA, Small Interfering (metabolism)
• Uridine Diphosphate Glucose Dehydrogenase (metabolism)
• Wound Healing
• Xenograft Model Antitumor Assays