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Br J Cancer. 2018 Jan;118(1):43-51. doi: 10.1038/bjc.2017.374. Epub 2017 Nov 7.

Targeting de novo lipogenesis as a novel approach in anti-cancer therapy.

Author information

  • 1Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University of Munich, Butenandstr. 5-13, Munich, Germany.
  • 2Nanosystems Initiative Munich (NIM), Schellingstraße 4, Munich, Germany.
  • 3Photonics and Optoelectronics Group, Department of Physics and Center for Nanoscience, Ludwig-Maximilians-University of Munich, Amalienstr. 54, Munich, Germany.
  • 4Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, Jena, Germany.
  • 5Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, Campus E8.1, Saarbrücken, Germany.

Abstract

BACKGROUND:

Although altered membrane physiology has been discussed within the context of cancer, targeting membrane characteristics by drugs being an attractive therapeutic strategy has received little attention so far.

METHODS:

Various acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) inhibitors (like Soraphen A and Cerulenin) as well as genetic knockdown approaches were employed to study the effects of disturbed phospholipid composition on membrane properties and its functional impact on cancer progression. By using state-of-the-art methodologies such as LC-MS/MS, optical tweezers measurements of giant plasma membrane vesicles and fluorescence recovery after photobleaching analysis, membrane characteristics were examined. Confocal laser scanning microscopy, proximity ligation assays, immunoblotting as well as migration, invasion and proliferation experiments unravelled the functional relevance of membrane properties in vitro and in vivo.

RESULTS:

By disturbing the deformability and lateral fluidity of cellular membranes, the dimerisation, localisation and recycling of cancer-relevant transmembrane receptors is compromised. Consequently, impaired activation of growth factor receptor signalling cascades results in abrogated tumour growth and metastasis in different in vitro and in vivo models.

CONCLUSIONS:

This study highlights the field of membrane properties as a promising druggable cellular target representing an innovative strategy for development of anti-cancer agents.

PMID:
29112683
PMCID:
PMC5765225
[Available on 2019-01-01]
DOI:
10.1038/bjc.2017.374
[PubMed - in process]
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