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Acetylation of alpha-fetoprotein promotes hepatocellular carcinoma progression.
- Source :
-
Cancer Letters . Feb2020, Vol. 471, p12-26. 15p. - Publication Year :
- 2020
-
Abstract
- Alpha-fetoprotein (AFP) is a well-established biomarker for hepatocellular carcinoma (HCC). Here, we investigated the acetylation state of AFP in vivo. AFP acetylation was regulated by the acetyltransferase CBP and the deacetylase SIRT1. Acetylation of AFP at lysines 194, 211, and 242 increased the stability of AFP protein by decreasing its ubiquitination and proteasomal degradation. AFP acetylation promoted its oncogenic role by blocking binding to the phosphatase PTEN and the pro-apoptotic protein caspase-3, which increased signaling for proliferation, migration, and invasion and decreased apoptosis. High levels of acetylated AFP in HCC tissues were associated with HBV infection and correlated with poor prognosis and decreased patient survival. In HCC cells, hepatitis B virus X protein (HBx) and palmitic acid (PA) increased the level of acetylated AFP by disrupting SIRT1-mediated deacetylation. AFP acetylation plays an important role in HCC progression and provides a new potential prognostic marker and therapeutic target for HCC. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ACETYLATION
*HEPATOCELLULAR carcinoma
*ALPHA fetoproteins
*PTEN protein
*HEPATITIS B virus
*PROTEIN metabolism
*AMINO acids
*ANIMAL experimentation
*APOPTOSIS
*CANCER invasiveness
*CELL physiology
*CELL motility
*COMPARATIVE studies
*EPITHELIAL cells
*FATTY acids
*GENETIC techniques
*LIVER tumors
*RESEARCH methodology
*MEDICAL cooperation
*METABOLISM
*MICE
*PROGNOSIS
*PROTEINS
*RESEARCH
*TRANSFERASES
*EVALUATION research
*CHRONIC hepatitis B
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 471
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 140919382
- Full Text :
- https://doi.org/10.1016/j.canlet.2019.11.043