PSPH promotes melanoma growth and metastasis by metabolic deregulation-mediated transcriptional activation of NR4A1.

ABSTRACT: Metabolic deregulation, a hallmark of cancer, fuels cancer cell growth and metastasis. Here, we show that phosphoserine phosphatase (PSPH), an enzyme of the serine metabolism pathway, is upregulated in patient-derived melanoma samples. PSPH knockdown using short hairpin RNAs (shRNAs) blocks melanoma tumor growth and metastasis in both cell culture and mice. To elucidate the mechanism underlying PSPH action, we evaluated PSPH shRNA-expressing melanoma cells using global metabolomics and targeted mRNA expression profiling. Metabolomics analysis showed an increase in 2-hydroxyglutarate (2-HG) levels in PSPH knockdown cells. 2-HG inhibits the TET family of DNA demethylases and the Jumonji family of histone demethylases (KDM and JMJD), which is known to impact gene expression. Consistent with t

SUBMITTER: Rawat V 

PROVIDER: S-EPMC8026604 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature