Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma.

Autor: Ueno T; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Otani S; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Date Y; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Katsuma Y; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Nagayoshi Y; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Ito T; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Ii H; Department of Clinical Oncology, Kyoto Pharmaceutical University, Kyoto, Japan., Kageyama S; Department of Urology, Shiga University of Medical Science, Otsu, Japan., Nakata S; Department of Clinical Oncology, Kyoto Pharmaceutical University, Kyoto, Japan., Ito K; Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2024 Sep; Vol. 115 (9), pp. 2961-2971. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1111/cas.16255
Abstrakt: Osteosarcoma (OS) in humans is characterized by alterations in the TP53 gene. In mice, loss of p53 triggers OS development, for which c-Myc (Myc) oncogenicity is indispensable. However, little is known about which genes are targeted by Myc to promote tumorigenesis. Here, we examined the role of γ-glutamylcyclotransferase (Ggct) which is a component enzyme of the γ-glutamyl cycle essential for glutathione homeostasis, in human and mouse OS development. We found that GGCT is a poor prognostic factor for human OS, and that deletion of Ggct suppresses p53-deficient osteosarcomagenesis in mice. Myc upregulates Ggct directly by binding to the Ggct promoter, and deletion of a Myc binding site therein by genome editing attenuated the tumorigenic potential of p53-deficient OS cells. Taken together, these results show a rationale that GGCT is widely upregulated in cancer cells and solidify its suitability as a target for anticancer drugs.
(© 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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