Integration of genetic and metabolic features related to sialic acid metabolism distinguishes human breast cell subtypes

PloS One
Christopher T SaeuiKevin J Yarema

Abstract

In this report we use 'high-flux' tributanoyl-modified N-acetylmannosamine (ManNAc) analogs with natural N-acetyl as well as non-natural azido- and alkyne N-acyl groups (specifically, 1,3,4-O-Bu3ManNAc, 1,3,4-O-Bu3ManNAz, and 1,3,4-O-Bu3ManNAl respectively) to probe intracellular sialic acid metabolism in the near-normal MCF10A human breast cell line in comparison with earlier stage T-47D and more advanced stage MDA-MB-231 breast cancer lines. An integrated view of sialic acid metabolism was gained by measuring intracellular sialic acid production in tandem with transcriptional profiling of genes linked to sialic acid metabolism. The transcriptional profiling showed several differences between the three lines in the absence of ManNAc analog supplementation that helps explain the different sialoglycan profiles naturally associated with cancer. Only minor changes in mRNA transcript levels occurred upon exposure to the compounds confirming that metabolic flux alone can be a key determinant of sialoglycoconjugate display in breast cancer cells; this result complements the well-established role of genetic control (e.g., the transcription of STs) of sialylation abnormalities ubiquitously associated with cancer. A notable result was t...Continue Reading

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Citations

Jun 19, 2018·Cancers·Emily Rodrigues, Matthew S Macauley
Dec 12, 2019·Advanced Materials·Vítor M GasparJoão F Mano
Nov 30, 2019·Nature Reviews. Chemistry·Christian AgatemorKevin J Yarema
Nov 20, 2018·Frontiers in Immunology·Matthew J BuettnerKevin J Yarema
Dec 1, 2020·The FEBS Journal·Heinz LäubliShoib Sarwar Siddiqui

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Methods Mentioned

BETA
glycosylation
flow cytometry
PCR
scraping
FACS

Software Mentioned

MATLAB
R

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