2020-06-10T05:24:22 n8324

Metabolic plasticity in cancer activates apocryphal pathways for lipid desaturation

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Abstract

Fatty acid (FA) modifications, such as enzymatic desaturation and elongation, have long been thought to involve sequential and highly specific enzyme-substrate interactions, which result in canonical products that are well-defined in their chain lengths, degree of unsaturation and double bond positions. These products act as a supply of building blocks for the synthesis of complex lipids supporting a symphony of lipid signals and membrane macrostructure. Recently, it was brought to light that differences in substrate availability due to enzyme inhibition can activate alternative pathways in a range of cancers, potentially altering the total species repertoire of FA metabolism. We have used isomer-resolved lipidomics to analyse human prostate tumours and cancer cell lines and that reveal, for the first-time, the full extent of metabolic plasticity in cancer. Assigning the double bond position(s) in simple and complex lipids allows mapping of fatty acid desaturation and elongation via hitherto apocryphal metabolic pathways that generate FAs with unusual sites of unsaturation. Downstream utilisation of these FAs is demonstrated by their incorporation into complex structural lipids. The unsaturation profiles of different phospholipids reveal substantive structural variation between classes that will, necessarily, modulate lipid-centred biological processes in cancer cells including membrane fluidity and signal transduction.

Access rights

The owner of this data collection reserves the right to provide access to the data by negotiation

Geographical area of data collection

text
MALDI-MSI-OzID: M4I, The Maastricht MultiModal Molecular Imaging Institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, MD, Maastricht, The Netherlands Direct infusion OzID and MSMS experiments: Central Analytical Research Facility, Institute for Future Environments, Queensland University of Technology, 2 George St, Brisbane, QLD 4000, Australia. Biological and patient samples/data: Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Princess Alexandra Hospital, Translational Research Institute, Brisbane 4000, Australia

Research areas

Biochemistry

Cite this collection

Young, Reuben; Bowman, Andrew; Williams, Elizabeth; Tousignant, Kaylyn; Bidgood, Charles; Narreddula, Venkateswara; Gupta, Rajesh; Marshall, David; Poad, Berwyck; Nelson, Colleen; Ellis, Shane; Heeren, Ron; Sadowski, Martin; Blanksby, Stephen (2020): Metabolic plasticity in cancer activates apocryphal pathways for lipid desaturation. Unpublished. (Dataset) https://doi.org/10.25912/5eddf867b9aee

Partner institution

M4I, Masstricht MultiModal Molecular Imaging Institute https://www.maastrichtuniversity.nl/research/m4i-division-imaging-mass-spectrometry

Licence


Creative Commons Attribution-NonCommercial-Share Alike 4.0 (CC-BY-NC-SA)
http://creativecommons.org/licenses/by-nc-sa/4.0/

Copyright

©Reuben S. E. Young, 2020

Dates of data collection

From 2018-02-12 to 2020-06-01

Connections

Has chief investigator
Stephen Blanksby  (Researcher)

Contacts

Name: Mr Reuben Young
Phone: 0431203226

Other

Date record created:
2020-06-05T15:44:01
Date record modified:
2020-06-10T05:24:22
Record status:
Published - Open Access