Proteomics

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Proteomic analysis of breast EMT cell models reveal UGDH is upregulated during EMT and holds the potential as a clinical target

ABSTRACT: Epithelial–mesenchymal transition (EMT) is known to be involved in cancer metastasis and pathogenesis. Metabolic re-wiring is now considered to be one of the hallmarks of cancer. In this study, we studied the metabolic changes during EMT in three breast EMT cell models with a proteomic approach. The study showed well-known changes during EMT including CDH1, CDH2, VIM, LGALS1, SERPINE1 and PKP3. It also suggested a list of dysregulated metabolic enzymes: SORD, TSTA3, FDFT1 and UGDH. UGDH had the biggest change and is associated with patient survival. We further studied the role of UGDH in EMT and found out knockdown of UGDH with siRNA can decrease the intracellular glycerophosphocholine level and it can also slow cell proliferation and invasion in mesenchymal cells. Besides, knockdown of UGDH downregulated the expression of a well-known EMT marker, SNAI1. PDGFRB is highly expressed in mesenchymal cells and PDGFD is highly secreted from mesenchymal cells. Knockdown of PDGFRB with siRNA downregulated UGDH potentially via NFkB.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Breast Cancer

SUBMITTER: Animesh Sharma  

LAB HEAD: Professor Óttar Rolfsson

PROVIDER: PXD024164 | Pride | 2022-01-04

REPOSITORIES: Pride

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Publications

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

Wang Qiong Q   Karvelsson Sigurdur Trausti ST   Johannsson Freyr F   Vilhjalmsson Arnar Ingi AI   Hagen Lars L   de Miranda Fonseca Davi D   Sharma Animesh A   Slupphaug Geir G   Rolfsson Ottar O  

Molecular oncology 20220203 9

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 metabo  ...[more]

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