Phosphoribosyl pyrophosphate amidotransferase: Novel biomarker and therapeutic target for nasopharyngeal carcinoma.

Autor: Kitagawa Y; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Kondo S; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Fukuyo M; Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan., Wakae K; Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan., Dochi H; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Mizokami H; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Komura S; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Kobayashi E; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Hirai N; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Ueno T; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Nakanishi Y; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Endo K; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Sugimoto H; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Wakisaka N; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan., Kaneda A; Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan., Yoshizaki T; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2024 Nov; Vol. 115 (11), pp. 3587-3595. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1111/cas.16314
Abstrakt: Cancer cells show a dynamic metabolic landscape, requiring a sufficient supply of nucleotides to proliferate. They are highly dependent on de novo purine biosynthetic pathways for their nucleotide requirements. Phosphoribosyl pyrophosphate amidotransferase (PPAT), catalyzing the first step of de novo purine biosynthesis, is highly expressed in various cancers. We observed an increased expression of PPAT in nasopharyngeal carcinoma (NPC). Moreover, our ribonucleic acid sequencing analysis showed high PPAT expression in Epstein-Barr virus-positive NPC, which was supported by in vitro analysis. Through a gene knockdown study, we showed that the suppression of PPAT expression reduced the proliferation and invasion of NPC cells. We also demonstrated the regulation of PPAT by glutamine, a cosubstrate for PPAT. A glutamine antagonist, 6-diazo-5-oxo-L-norleucine, blocked glutamine-mediated induction of PPAT and reduced NPC cell proliferation. Immunohistochemical analysis of PPAT in NPC tissues revealed increased expression of PPAT with disease progression, which was significantly associated with poor prognosis. In summary, this study highlighted the biological function of PPAT in NPC, establishing its potential as a novel prognostic biomarker for aggressive NPC and a promising therapeutic target.
(© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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