Phosphoproteome profiling revealed abnormally phosphorylated AMPK and ATF2 involved in glucose metabolism and tumorigenesis of GH-PAs

Abstract

Purpose

Protein phosphorylation plays a key role in tumorigenesis and progression. However, little is known about the phosphoproteome profiles of growth hormone-secreting pituitary adenomas (GH-PAs). The aim of this study was to identify critical biomarkers and signaling pathways that might play important roles in GH-PAs and may, therefore, represent potential therapeutic targets.

Methods

The differential phosphoprotein expression patterns involved in GH-PAs were investigated by nano-LC–MS/MS in a group of samples. The phosphoprotein expression data were analyzed by bioinformatics. The expression levels of the candidate phosphorylated AMPK (ser496) and ATF2 (ser112) were validated by Western blot analysis in another group of samples.

Results

A total of 1213 phosphorylated protein sites corresponding to 667 proteins were significantly different between GH-PAs and healthy pituitary glands. Among these phosphorylated sites, 871 exhibited lower levels of phosphorylation in GH-PAs. Moreover, 140 novel phosphosites corresponding to 93 proteins were differentially phosphorylated between GH-PAs and healthy pituitary glands, 101 of which showed decreased phosphorylation in GH-PAs. The majority of differentially expressed phosphorylated proteins were significantly enriched in glycolysis and the AMPK signaling pathway in GH-PAs. The AMPK signaling pathway was demonstrated to be inhibited in GH-PAs by pathway activity analysis (z score = − 2.324). Notably, the phosphorylated levels of AMPK (ser496) and ATF2 (ser112) were significantly lower in GH-PAs than in healthy pituitary glands.

Conclusion

These findings suggest that decreased phosphorylation of the AMPK/ATF2 pathway may be critical for glucose metabolism and tumorigenesis in GH-PAs.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2K9PQJy