Acetylation of alpha-fetoprotein promotes hepatocellular carcinoma progression.

Authors :: Xue J
Cao Z
Cheng Y
Wang J
Liu Y
Yang R
Li H
Jiang W
Li G
Zhao W
Zhang X
Source :: Cancer letters [Cancer Lett] 2020 Feb 28; Vol. 471, pp. 12-26. Date of Electronic Publication: 2019 Dec 05.
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.<br /> (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)