Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1021/acs.jproteome.7b00782
Title (Primary) Deletion of adipose triglyceride lipase links triacylglycerol accumulation to a more-aggressive phenotype in A549 lung carcinoma cells
Author Tomin, T.; Fritz, K.; Gindlhuber, J.; Waldherr, L.; Pucher, B.; Thallinger, G.G.; Nomura, D.K.; Schittmayer, M.; Birner-Gruenberger, R.
Source Titel Journal of Proteome Research
Year 2018
Department MOLSYB
Volume 17
Issue 4
Page From 1415
Page To 1425
Language englisch
Supplements https://pubs.acs.org/doi/suppl/10.1021/acs.jproteome.7b00782/suppl_file/pr7b00782_si_004.pdf
Keywords A549 lung carcinoma cells; ATGL; cancer; lipid droplet; migration; SRC; triacylglycerol
UFZ wide themes RU3;
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.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=20217
Tomin, T., Fritz, K., Gindlhuber, J., Waldherr, L., Pucher, B., Thallinger, G.G., Nomura, D.K., Schittmayer, M., Birner-Gruenberger, R. (2018):
Deletion of adipose triglyceride lipase links triacylglycerol accumulation to a more-aggressive phenotype in A549 lung carcinoma cells
J. Proteome Res. 17 (4), 1415 - 1425