Altered cellular metabolism is a hallmark of tumor cells since they must adapt their metabolic machinery to increase proliferation. Adipose triglyceride lipase (ATGL) catalyzes the initial step in triglyceride hydrolysis thus providing fatty acids as building blocks for biomass as well as an energy source. We have recently discovered that ATGL expression is lost early in the development of human pancreatic cancer and is virtually absent in the majority of adencarcinoma of the lung as well as in leiomyosarcoma. Remarkeably, experimental Bcr-Abl translocation positive B-cell lymphomas that are deficient in ATGL exhibit a dramatically increased growth rate and aggressive metastatic behaviour. Similar effects were observed in Lewis Lung Carcinoma and B16F10 melanoma cells transfected with an ATGL regulatory shRNA. In mice, ATGL-/- tumors showed enhanced angiogenesis and reduced T-cell infiltration. Based on these observations we postulate that ATGL might function as a metabolic tumor suppressor.

Cancer-associated cachexia is characterized by a profound loss of adipose tissue and skeletal muscle wasting that frequently complicates malignancies and accounts for about 20% of cancer deaths. We have recently published that inhibition of lipolysis through genetic ablation of ATGL or hormone-sensitive lipase (HSL) prevents or reduces cancer-associated cachexia in mice. Remarkably, we could also correlate the severity of cachexia with ATGL activity in white adipose tissue of cancer patients. Furthermore, cachexia is correlated to tumor size and possibly to loss of ATGL expression in experimental B-cell tumors.

Our students aim at elucidating the pathogenetic connection of lipase activity leading to tumor growth and initiation and investigate the mechanism(s) leading to downregulation of ATGL expression in cancer development.

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