Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells

Tamara Tomin, Katarina Fritz, Juergen Gindlhuber, Linda Waldherr, Bettina Pucher, Gerhard G Thallinger, Daniel K Nomura, Matthias Schittmayer, Ruth Birner-Gruenberger

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1415-1425
JournalJournal of proteome research
Volume17
Issue number4
DOIs
Publication statusPublished - 6 Apr 2018

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Lipase
Triglycerides
Cells
Carcinoma
Phenotype
Lung
Phosphotransferases
Lipids
Neoplasms
Phospholipid Ethers
Clustered Regularly Interspaced Short Palindromic Repeats
Oncogenes
Adipocytes
Proteomics
Labels
Tumors
Lung Neoplasms
Phospholipids
Western Blotting
Chemical activation

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Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells. / Tomin, Tamara; Fritz, Katarina; Gindlhuber, Juergen; Waldherr, Linda; Pucher, Bettina; Thallinger, Gerhard G; Nomura, Daniel K; Schittmayer, Matthias; Birner-Gruenberger, Ruth.

In: Journal of proteome research, Vol. 17, No. 4, 06.04.2018, p. 1415-1425.

Research output: Contribution to journalArticleResearchpeer-review

Tomin, T, Fritz, K, Gindlhuber, J, Waldherr, L, Pucher, B, Thallinger, GG, Nomura, DK, Schittmayer, M & Birner-Gruenberger, R 2018, 'Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells' Journal of proteome research, vol. 17, no. 4, pp. 1415-1425. https://doi.org/10.1021/acs.jproteome.7b00782
Tomin, Tamara ; Fritz, Katarina ; Gindlhuber, Juergen ; Waldherr, Linda ; Pucher, Bettina ; Thallinger, Gerhard G ; Nomura, Daniel K ; Schittmayer, Matthias ; Birner-Gruenberger, Ruth. / Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells. In: Journal of proteome research. 2018 ; Vol. 17, No. 4. pp. 1415-1425.
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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.",
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AU - Fritz, Katarina

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AU - Waldherr, Linda

AU - Pucher, Bettina

AU - Thallinger, Gerhard G

AU - Nomura, Daniel K

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N2 - 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.

AB - 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.

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