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

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.

Role and mechanism of FDFT1 in regulating ferroptosis in colon cancer cells via the Nrf2/GPX4 pathway

“…Alterations in FDFT1 expression are usually observed in cancer, including regulation of non-coding RNAs, and overexpression of FDFT1 suppresses ovarian cancer by decreasing miR-4425 [27]. Due to the important role of FDFT1 in tumor progression, it is expected to be a target for anticancer therapy [28]. FDFT1 is located on chromosome 8p23.1 (Chromosome 8-NC_000008.11), and FDFT1 is associated with a positive prognosis in ovarian cancer [27].…”

Exploring the prognostic features and immune landscape of exosome-related genes in breast cancer metastasis based on bioinformatics methods

“…In the cell model of epithelial-mesenchymal transition (EMT) of BRCA metastasis, researchers explored the changes of protein omics during spontaneous EMT. They determined that proteins such as JUP participated in the EMT procedure and may participate in normal human breast development [13].…”

MTCH2 in Metabolic Diseases, Neurodegenerative Diseases, Cancers, Embryonic Development and Reproduction

“… 85 Similarly, the involvement of MTCH2 in normal human breast gland development might result in the association of MTCH2 with the epithelial–mesenchymal transition in breast cancer. 86 However, the protein level of MTCH2 is increased 2.3 times in breast tumor MDA-MB-231 cell line after treatment with sub-toxic dose of snake venom compared with untreated cells. 87 MTCH2 expression reduces Met-HGF/SF-induced proliferation and scattering by attenuating and altering the downstream signaling of Met in breast cancer cell lines.…”