NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor-Negative Breast Cancer.

Molecular & Cellular Proteomics : MCP
Rikke LundHenrik J Ditzel

Abstract

Metastasis is the main cause of cancer-related deaths and remains the most significant challenge to management of the disease. Metastases are established through a complex multistep process involving intracellular signaling pathways. To gain insight to proteins central to specific steps in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using stable isotopic labeling by amino acids in cell culture and subcellular fractionation, the nuclear, cytosol, and mitochondria proteomes were analyzed by LC-MS/MS, identifying a number of proteins that exhibited altered expression in isogenic metastatic versus nonmetastatic cancer cell lines, including NADH-cytochrome b5 reductase 3 (CYB5R3), l-lactate dehydrogenase A (LDHA), Niemann-pick c1 protein (NPC1), and nucleolar RNA helicase 2 (NRH2). The altered expression levels were validated at the protein and transcriptional levels, and analysis of breast cancer biopsies from two cohorts of patients demonstrated a significant correlation between high CYB5R3 expression and poor disease-free and overall survival in patients with estrogen receptor-negative tumors (DFS: p = .02, OS:...Continue Reading

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Citations

Jul 5, 2016·The International Journal of Biochemistry & Cell Biology·Alessandro RimessiPaolo Pinton
Sep 25, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Mohd MugheesSaima Wajid
May 16, 2020·Oxidative Medicine and Cellular Longevity·Rumiana BakalovaTatsuya Higashi
Jun 6, 2019·Scientific Reports·Michael StuelandStavroula Mili
Oct 5, 2020·Endocrine·Elena V ProskurninaEvgeny V Svetlov

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