Abstract 164P
Background
Breast cancer is the most frequent cancer in women and the leading cause of women cancer death worldwide yet. A common feature of cancer cells is reprogramming of fatty acid metabolism which constitutes an adaptive mechanism but also a targetable weakness. We were interested in Elongate of very long chain fatty acid protein 5 (ELOVL5) which catalyzes the addition of two carbons to the chain of long-chain fatty acids. Indeed, the analysis of Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset showed a poor overall survival in breast cancer patients with low expression of ELOVL5.
Methods
We developed in vitro and in vivo approaches for evaluating the role of ELOVL5 in breast cancer progression.
Results
Full ELOVL5 knockout (KO) in mouse mammary carcinoma model MMTV-PyMT resulted in a delay of tumor onset and a decrease of tumor growth. In vitro experiments confirmed that ELOVL5 knock-down in mouse 4T1 (triple-negative breast cancer cells) and human MCF-7 (ER+ breast cancer cells) with siRNA strategy inhibited cancer cell proliferation. By contrast, ELOVL5-overexpressing 4T1 cells proliferated faster and ELOVL5-overexpressing 4T1-bearing mice developed larger tumors. Moreover, we observed accumulation of lipid droplets in ELOVL5 -silenced cancer cells and we demonstrated that ablation of lipid droplet accumulation with pharmacological inhibitors of Diacylglycerol acyltransferases counteracted the inhibition of proliferation induced by ELOVL5 silencing.
Conclusions
Altogether our study suggested an evidencee that ELOVL5 controlled cell proliferation and breast cancer progression. Therefore, ELOVL5 might be a new target in breast cancer treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
La Ligue Contre le Cancer, LabEx LipSTIC, Universite de Bourgogne, INSERM U1231.
Disclosure
All authors have declared no conflicts of interest.