Targeting UDP‐glucose dehydrogenase inhibits ovarian cancer growth and metastasis

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 20; pp. 11883 - 11902
• Main Authors: Lin, Li‐Hsun, Chou, Hsiu‐Chuan, Chang, Shing‐Jyh, Liao, En‐Chi, Tsai, Yi‐Ting, Wei, Yu‐Shan, Chen, Hsin‐Yi, Lin, Meng‐Wei, Wang, Yi‐Shiuan, Chien, Yu‐An, Yu, Xin‐Ru, Chan, Hong‐Lin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2020; John Wiley and Sons Inc
• Subjects: Actins - metabolism; Animals; Antibodies; Breast cancer; Cancer therapies; Cell adhesion & migration; Cell cycle; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Dehydrogenases; EMT; Epithelial-Mesenchymal Transition; ERK; Female; G1 phase; G1 Phase Cell Cycle Checkpoints; Gelatinase A; Gene Knockdown Techniques; Glucose; Glucose dehydrogenase; Humans; Immunoglobulins; Invasiveness; Kinases; Lung cancer; MAP kinase; MAP Kinase Signaling System; Medical prognosis; Mesenchyme; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; Models, Biological; Mortality; Neoplasm Invasiveness; Neoplasm Metastasis; Original; Ovarian cancer; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Penicillin; Polymerization; Proteins; Proteomics; RNA, Small Interfering - metabolism; RNA-mediated interference; Signal transduction; Tumors; UGDH; Uridine Diphosphate Glucose Dehydrogenase - metabolism; Wound Healing; Xenograft Model Antitumor Assays; Taiwan; UGDH; metastasis; ovarian cancer; EMT; ERK
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.15808

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.