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Deregulation of acetyl-CoA metabolism reduces global acetylation in HCC

Research Project
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01.04.2021
 - 30.11.2021

Hepatocellular carcinoma (HCC) is a major health problem with more than 850,000 new cases annually and the 4th leading cause of cancer deaths worldwide, due to the limited therapeutic options and late diagnosis. It is well known that cellular metabolism is dramatically changed during tumorigenesis. However, the mechanisms underlying deregulation mechanism of metabolic enzymes have not been studied in depth. We found that acetyl-CoA metabolism is significantly downregulated in an mTOR driven HCC mouse model and in human HCC patients. Acetyl-CoA is an essential metabolite that is involved in many metabolic conversions and cellular functions, including regulation of gene transcription by histone acetylation and de novo fatty acid synthesis. Protein acetylation relies on the availability of acetyl-CoA, the levels of which can change depending on metabolic conditions. In cancer, oncogenic signaling pathways reprogram cellular metabolism and affect acetyl-CoA levels. However, acetyl-CoA availability and protein acetylation status, especially non-histone acetylation during tumorigenesis is unknown. Our unpublished data indicate that deregulation of acetyl-CoA homeostasis and global protein acetylation in HCC due to downregulation of acetyl-CoA production pathways. Furthermore, we identified transcriptional regulators that are induced during tumorigenesis and negatively control expression of enzymes in acetyl-CoA production pathways. Moreover, modulation of these transcriptional regulators affects proliferation of cancer cells. Our findings suggest that deregulation of acetyl-CoA metabolism and global acetylation is a hallmark of liver tumorigenesis and correlates with the aggressiveness of tumour. Our findings may lead to new strategies for the treatment of HCC.

Funding

Deregulation of acetyl-CoA metabolism reduces global acetylation in HCC

Forschungsfonds (Excellent Junior Researcher) (GrantsTool), 04.2021-11.2021 (8)
PI : Park, Sujin.
CI : Hall, Michael N..

Members (2)

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Sujin Park

Principal Investigator
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Michael N. Hall

Co-Investigator