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UDP-glucose dehydrogenase expression is upregulated following EMT and differentially affects intracellular glycerophosphocholine and acetylaspartate levels in breast mesenchymal cell lines

UDP-glucose dehydrogenase expression is upregulated following EMT and differentially affects intracellular glycerophosphocholine and acetylaspartate levels in breast mesenchymal cell lines


Title: UDP-glucose dehydrogenase expression is upregulated following EMT and differentially affects intracellular glycerophosphocholine and acetylaspartate levels in breast mesenchymal cell lines
Author: Wang, Qiong
Karvelsson, Sigurdur Trausti
Johannsson, Freyr
Vilhjalmsson, Arnar Ingi
Hagen, Lars
de Miranda Fonseca, Davi
Sharma, Animesh
Slupphaug, Geir
Rolfsson, Ottar
Date: 2022-05
Language: English
Scope: 25
Department: Faculty of Medicine
Series: Molecular Oncology; 16(9)
ISSN: 1574-7891
DOI: https://doi.org/10.1002/1878-0261.13172
Subject: acetylaspartate; breast cancer; EMT; glycerophosphocholine; PDGFRB; UGDH; Breast Neoplasms/pathology; Humans; Receptor, Platelet-Derived Growth Factor beta; Ketone Oxidoreductases; Uridine Diphosphate Glucose Dehydrogenase/metabolism; Epithelial-Mesenchymal Transition/genetics; Uridine Diphosphate; Glucose Dehydrogenases; Proteomics; Cell Line, Tumor; Female; RNA, Small Interfering; Carbohydrate Epimerases; Genetics; Molecular Medicine; Oncology; Cancer Research
URI: https://hdl.handle.net/20.500.11815/3829

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Citation:

Wang , Q , Karvelsson , S T , Johannsson , F , Vilhjalmsson , A I , Hagen , L , de Miranda Fonseca , D , Sharma , A , Slupphaug , G & Rolfsson , O 2022 , ' UDP-glucose dehydrogenase expression is upregulated following EMT and differentially affects intracellular glycerophosphocholine and acetylaspartate levels in breast mesenchymal cell lines ' , Molecular Oncology , vol. 16 , no. 9 , pp. 1816-1840 . https://doi.org/10.1002/1878-0261.13172

Abstract:

Metabolic rewiring is one of the indispensable drivers of epithelial–mesenchymal transition (EMT) involved in breast cancer metastasis. In this study, we explored the metabolic changes during spontaneous EMT in three separately established breast EMT cell models using a proteomic approach supported by metabolomic analysis. We identified common proteomic changes, including the expression of CDH1, CDH2, VIM, LGALS1, SERPINE1, PKP3, ATP2A2, JUP, MTCH2, RPL26L1 and PLOD2. Consistently altered metabolic enzymes included the following: FDFT1, SORD, TSTA3 and UDP-glucose dehydrogenase (UGDH). Of these, UGDH was most prominently altered and has previously been associated with breast cancer patient survival. siRNA-mediated knock-down of UGDH resulted in delayed cell proliferation and dampened invasive potential of mesenchymal cells and downregulated expression of the EMT transcription factor SNAI1. Metabolomic analysis revealed that siRNA-mediated knock-down of UGDH decreased intracellular glycerophosphocholine (GPC), whereas levels of acetylaspartate (NAA) increased. Finally, our data suggested that platelet-derived growth factor receptor beta (PDGFRB) signalling was activated in mesenchymal cells. siRNA-mediated knock-down of PDGFRB downregulated UGDH expression, potentially via NFkB-p65. Our results support an unexplored relationship between UGDH and GPC, both of which have previously been independently associated with breast cancer progression.

Description:

Funding Information: The study received funding from Icelandic centre for research award number: 163254‐051; Recipient: Ottar Rolfsson and Doktorsstyrkir Háskóla Ísland; Doktorsstyrkir 2020; Recipient: Qiong Wang. Publisher Copyright: © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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