Targeting De Novo Lipogenesis As a Novel Approach in Anti-cancer Therapy

Overview

Journal Br J Cancer

Specialty Oncology

Date 2017 Nov 8

PMID 29112683

Citations 27

Authors

Katharina Stoiber

Olga Naglo

Carla Pernpeintner

Siwei Zhang

Andreas Koeberle

Melanie Ulrich

Oliver Werz

Rolf Muller

Stefan Zahler

Theobald Lohmuller

Jochen Feldmann

Simone Braig

Affiliations

Soon will be listed here.

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.

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