ArticleOncogene2021
PSPH promotes melanoma growth and metastasis by metabolic deregulation-mediated transcriptional activation of NR4A1.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- PSPH Promotes Hepatocellular Carcinoma Progression by Upregulating HIF-1α and Is Regulated by LncRNA GSEC/miR-101-3p.Current issues in molecular biology · 2026Article
- IGF2BP2-driven serine metabolism promotes the progression of thyroid carcinoma via mJournal of translational medicine · 2026Article
- Research based on serine metabolism indicates mesenchymal stem cells alleviate psoriasis by regulating the PSPH-PINK1-Parkin-NLRP3 pathway in HaCaT.Stem cell research & therapy · 2026Article
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- The mechanism of PKM2/HIF-1α axis polarizing TAMs by upregulating glucose-serine metabolism to promote melanoma progression.Frontiers in immunology · 2026Article
- NRF2-SOX4 complex regulates PSPH in hepatocellular carcinoma and modulates M2 macrophage differentiation.Cancer gene therapy · 2025Article
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
- Serine metabolism in tumor progression and immunotherapy.Discover oncology · 2025Review
- Abnormal changes in metabolites caused by mJournal of advanced research · 2025Review
- Targeting the nuclear orphan receptor NR4A1: a key target in lung cancer progression and therapeutic resistance.Frontiers in oncology · 2025Review
- The role and research progress of serine metabolism in tumor cells.Frontiers in oncology · 2025Review
- PSPH promotes the proliferation and metastasis of esophageal squamous cell carcinoma through MAPK signaling pathways.American journal of cancer research · 2025Article
- Recent progress in serine metabolism reprogramming in tumors and strategies for serine deprivation.Frontiers in oncology · 2025Review
- Metabolic insights into tumor lymph node metastasis in melanoma.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- L-serine deficiency: on the properties of the Asn133Ser variant of human phosphoserine phosphatase.Scientific reports · 2024Article
- Metabolic heterogeneity in cancer.Nature metabolism · 2024Review
- Integrative analysis of proteomics and lipidomic profiles reveal the fat deposition and meat quality in Duroc × Guangdong small spotted pig.Frontiers in veterinary science · 2024Article
- Overcoming EGFR inhibitor resistance in Glioblastoma by targeting co-amplified genes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
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 these data, PSPH knockdown in melanoma cells showed reduced DNA 5-hydroxymethylcytosine (5hmC) and increased histone H3K4me3 modifications. 2-HG treatment also inhibited melanoma growth. The nCounter PanCancer Pathways Panel-based mRNA expression profiling revealed attenuation of a number of cancer-promoting pathways upon PSPH knockdown. In particular, PSPH was necessary for nuclear receptor NR4A1 expression. Ectopic NR4A1 expression partly rescued the growth of melanoma cells expressing PSPH shRNA. Collectively, these results link PSPH to the facilitation of melanoma growth and metastasis through suppression of 2-HG and thus activation of pro-oncogenic gene expression.
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