PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation mediated gene expression.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (PDH, E1), leaving other post-translational modifications (PTMs) largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma (HCC), disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression.

OXCT1 functions as a succinyltransferase, contributing to hepatocellular carcinoma via succinylating LACTB.

Metabolic reprogramming is an important feature of cancers that has been closely linked to post-translational protein modification (PTM). Lysine succinylation is a recently identified PTM involved in regulating protein functions, whereas its regulatory mechanism and possible roles in tumor progression remain unclear. Here, we show that OXCT1, an enzyme catalyzing ketone body oxidation, functions as a lysine succinyltransferase to contribute to tumor progression.

PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation.

Tumor metabolic reprogramming and epigenetic modification work together to promote tumorigenesis and development. Protein lysine acetylation, which affects a variety of biological functions of proteins, plays an important role under physiological and pathological conditions. Here, through immunoprecipitation and mass spectrum data, we show that phosphoglycerate mutase 5 (PGAM5) deacetylation enhances malic enzyme 1 (ME1) metabolic enzyme activity to promote lipid synthesis and proliferation of liver cancer cells.

pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate for targeted synergistic cancer therapy.

To promote the targeted cancer therapy, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate was successfully constructed. Herein, water-soluble vitamin B6 with pKa (5.6) was chemically conjugated to lipid-soluble vitamin E succinate (α-TOS), which showed selective cancer cell killing ability and this amphiphilic small molecule vitamin conjugate could self-assemble to be free nanoparticles (NPs) and doxorubicin-loaded NPs (α-TOS-B6-NPs-DOX).