Student Posters 51st Lorne Proteins Conference 2026

Computational Lipidomics Reveals Environment-Specific Membrane Remodeling in Prostate Cancer (#132)

Yumeng Hao 1 , Billy J. Williams-Noonan 1 , Patrick Sutton 1 , Reuben S.E. Young 2 3 , Stephen J. Blanksby 3 4 , Evelyne Deplazes 5 , Megan L. O'Mara 1
  1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia , QLD, Australia
  2. Molecular Horizons and School of Science, The University of Wollongong, Wollongong, NSW, Australia
  3. School of Chemistry and Physics, Queensland University of Technology, Brisbane, QLD , Australia
  4. Central Analytical Research Facility, Institute for Future Environments , Queensland University of Technology, 2 George St., Brisbane, QLD, Australia
  5. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia

Metabolic changes during cancer progression produce key differences in phospholipid distributions between normal (RWPE-1), benign hyperplasia (BPH-1) and metastatic prostate (lymph: LNCaP, bone: PC3, brain: DU-145) cell lines that are markers of disease progression and cancer cell adaptation.(1) The effect of cancer-associated lipidome shifts on membrane structural dynamics has not been investigated in a cell-specific context. Here we spatially map the specific membrane lipidome from each cell line dataset to assess membrane organization and dynamics in normal, benign hyperplasia, and metastatic prostate cell lines. Long timescale molecular dynamics simulations show leaflet-specific alterations in membrane dynamics, with increased fluidity in the intracellular leaflet of metastatic membranes. All membranes exhibited phase separated domains enriched in polyunsaturated lipids and depleted in cholesterol, however the extent of phase separation varied with disease state. Specifically, the loss of phosphatidylserine (PS) lipid leaflet asymmetry in metastatic cell membranes decreased phospholipid phase separation. In particular, the metastatic LNCaP showed exaggerated phase separation for distinct phospholipid species compared to all other metastatic and non-cancerous lines. These alterations in lipid co-localization and phase separation patterns across prostate cancer cell lines suggest environment-specific adaptations which may play a role in cancer progression.

  1. (1) Young, R. S. E.; Bowman, A. P.; Williams, E. D.; Tousignant, K. D.; Bidgood, C. L.; Narreddula, V. R.; Gupta, R.; Marshall, D. L.; Poad, B. L. J.; Nelson, C. C.; et al. Apocryphal FADS2 activity promotes fatty acid diversification in cancer. Cell Reports 2021, 34 (6), 108738. DOI: 10.1016/j.celrep.2021.108738.