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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Tomin, T; Fritz, K; Gindlhuber, J; Waldherr, L; Pucher, B; Thallinger, GG; Nomura, DK; Schittmayer, M; Birner-Gruenberger, R.
Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells.
J Proteome Res. 2018; 17(4):1415-1425 Doi: 10.1021/acs.jproteome.7b00782
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Führende Autor*innen der Med Uni Graz
Birner-Grünberger Ruth
Tomin Tamara
Co-Autor*innen der Med Uni Graz
Fritz Katarina
Gindlhuber Jürgen
Schittmayer-Schantl Matthias
Waldherr Linda
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Abstract:
Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here, we report that loss of ATGL supports a more-aggressive cancer phenotype in a model system in which ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label-free quantitative proteomics revealed elevated expression of the pro-oncogene SRC kinase in ATGL depleted cells, which was also found on mRNA level and confirmed on protein level by Western blot. Consistently, higher expression of phosphorylated (active) SRC (Y416 phospho-SRC) was observed in ATGL-KO cells. Cells depleted of ATGL migrated faster, which was dependent on SRC kinase activity. We propose that loss of ATGL may thus increase cancer aggressiveness by activation of pro-oncogenic signaling via SRC kinase and increased levels of bioactive lipids.

Find related publications in this database (Keywords)
ATGL
SRC
cancer
migration
lipid droplet
triacylglycerol
A549 lung carcinoma cells
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