Targeting UDP-α-d-glucose 6-dehydrogenase inhibits glioblastoma growth and migration

Olutobi Oyinlade, Shuang Wei, Bachchu Lal, John Laterra, Heng Zhu, C. Rory Goodwin, Shuyan Wang, Ding Ma, Jun Wan, Shuli Xia

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


UDP-glucose 6-dehydrogenase (UGDH) produces UDP-α-d-glucuronic acid, the precursors for glycosaminoglycans (GAGs) and proteoglycans of the extracellular matrix. Elevated GAG formation has been implicated in a variety of human diseases, including glioblastoma (GBM). In our previous study, we found that Krüppel-like factor 4 (KLF4) promotes GBM cell migration by binding to methylated DNA, mainly methylated CpGs (mCpG) and transactivating gene expression. We identified UDGH as one of the downstream targets of KLF4-mCpG binding activity. In this study, we show that KLF4 upregulates UGDH expression in a mCpG-dependent manner, and UGDH is required for KLF4-induced cell migration in vitro. UGDH knockdown decreases GAG abundance in GBM cells, as well as cell proliferation and migration in vitro. In intracranial xenografts, reduced UGDH inhibits tumor growth and migration, accompanied by a decrease in the expression of extracellular matrix proteins such as tenascin C, brevican. Our studies demonstrate a novel DNA methylation-dependent UGDH upregulation by KLF4. Developing UGDH antagonists to decrease the synthesis of extracellular matrix components will be a useful strategy for GBM therapy.

Original languageEnglish (US)
Pages (from-to)2615-2629
Number of pages15
Issue number20
StatePublished - May 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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