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

Oncogene
Olutobi OyinladeShuli Xia

Abstract

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.

References

Jul 1, 1994·Nature Genetics·J M Craig, W A Bickmore
Jul 2, 2004·Nature Reviews. Cancer·Bryan P Toole
Feb 1, 2008·Molecular Cancer Research : MCR·Thomas E ReznikJohn Laterra
Mar 6, 2009·Cell Adhesion & Migration·Jong Bae ParkSeung-Hoon Lee
Jun 27, 2009·Expert Opinion on Investigational Drugs·Cory AdamsonDarell D Bigner
Sep 25, 2010·Biochemical Society Transactions·Sigrid EggerBernd Nidetzky
Sep 16, 2011·Cold Spring Harbor Perspectives in Biology·Pengfei LuZena Werb
Feb 16, 2012·The FEBS Journal·Nikos AfratisNikos K Karamanos
Feb 22, 2012·The Journal of Cell Biology·Pengfei LuZena Werb
Jan 4, 2013·The FEBS Journal·Anna WadeJoanna J Phillips
Mar 29, 2014·BMC Genomics·Yulia A MedvedevaUNKNOWN FANTOM consortium
Apr 9, 2014·Cancer Research·Jessica TilghmanMingyao Ying
Nov 6, 2015·Frontiers in Oncology·Freja A VenningJanine T Erler
May 20, 2017·Current Medicinal Chemistry·Ron BatashMoshe Schaffer

❮ Previous
Next ❯

Citations

Mar 23, 2019·Oncotarget·C Rory GoodwinShuli Xia
Aug 5, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Brenna M ZimmerMelanie A Simpson
Jul 11, 2020·Nature Reviews. Materials·Kayla J WolfSanjay Kumar
Sep 8, 2020·Journal of Cellular and Molecular Medicine·Li-Hsun LinHong-Lin Chan
Feb 26, 2021·Nature·Diana MahdessianEmma Lundberg
Jun 15, 2021·Frontiers in Oncology·Wanyan WangJin Huang
Dec 9, 2021·Advanced Healthcare Materials·Chaitanya Tondepu, Lohitash Karumbaiah

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
RNA-seq
nucleotide exchange
ChIP-PCR
xenografts
xenograft
FCS
electrophoresis
immunoprecipitation
ChIP

Software Mentioned

REMBRANT
GraphPad
CellQuest
MCID
Prizm
ImageJ
Axiovision

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.