ArticleBiology direct2023
p63 orchestrates serine and one carbon metabolism enzymes expression in head and neck cancer.
Article in Biology direct, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Extracellular serine availability regulates inflammatory skin phenotypes.Biology direct · 2026Article
- ΔNp63α drives serine synthesis to promote carboplatin resistance in NSCLC.Cell death & disease · 2026Article
- PHGDH knockdown activates autophagic flux to suppress migration and invasion of gastric cancer cells.Translational cancer research · 2026Article
- In vitro synergistic effect of AXL, FAK and ErbB receptors inhibitors for head and neck cancer.Biology direct · 2025Article
- Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.Biology direct · 2024Article
- p63 affects distinct metabolic pathways during keratinocyte senescence, evaluated by metabolomic profile and gene expression analysis.Cell death & disease · 2024Article
- A comprehensive molecular characterization of a claudin-low luminal B breast tumor.Biology direct · 2024Article
- Molecular profiling of a bladder cancer with very high tumour mutational burden.Cell death discovery · 2024Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHead and neck squamous cell carcinoma (HNSCC) is characterized by high proliferation and limited differentiation. The altered expression of the p53 family members, and specifically of p63, represents a pivotal event in the pathogenesis of HNSCC. Physiologically, p63 affects metabolism through the direct transactivation of the enzyme hexokinase 2, and subsequently controls the proliferation of epithelial cells; nonetheless, its role in cancer metabolism is still largely unclear. The high energetic demand of cancer and the consequent needs of a metabolic reshape, also involve the serine and glycine catabolic and anabolic pathways, including the one carbon metabolism (OCM), to produce energetic compounds (purines) and to maintain cellular homeostasis (glutathione and S-adenosylmethionine).
resultsThe involvement in serine/glycine starvation by other p53 family members has been reported, including HNSCC. Here, we show that in HNSCC p63 controls the expression of the enzymes regulating the serine biosynthesis and one carbon metabolism. p63 binds the promoter region of genes involved in the serine biosynthesis as well as in the one carbon metabolism. p63 silencing in a HNSCC cell line affects the mRNA and protein levels of these selected enzymes. Moreover, the higher expression of TP63 and its target enzymes, negatively impacts on the overall survival of HNSCC patients.
conclusionThese data indicate a direct role of p63 in the metabolic regulation of HNSCC with significant clinical effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.