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WDR74 modulates melanoma tumorigenesis and metastasis through the RPL5–MDM2–p53 pathway

Publié dansOncogene, vol. 39, no. 13, p. 2741-2755
Date de publication2020
Résumé

The key molecules and underlying mechanisms of melanoma metastasis remain poorly understood. Using isobaric tag for relative and absolute quantitation (iTRAQ) proteomic screening, probing of patients' samples, functional verification, and mechanistic validation, we identified the important role of the WD repeat-containing protein 74 (WDR74) in melanoma progression and metastasis. Through gain- and loss-of-function approaches, WDR74 was found to promote cell proliferation, apoptosis resistance, and aggressive behavior in vitro. Moreover, WDR74 contributed to melanoma growth and metastasis in vivo. Mechanistically, WDR74 modulates RPL5 protein levels and consequently regulates MDM2 and insulates the ubiquitination degradation of p53 by MDM2. Our study is the first to reveal the oncogenic role of WDR74 in melanoma progression and the regulatory effect of WDR74 on the RPL5–MDM2-p53 pathway. Collectively, WDR74 can serve as a candidate target for the prevention and treatment of melanoma in the clinic.

Citation (format ISO)
LI, Yumei et al. WDR74 modulates melanoma tumorigenesis and metastasis through the RPL5–MDM2–p53 pathway. In: Oncogene, 2020, vol. 39, n° 13, p. 2741–2755. doi: 10.1038/s41388-020-1179-6
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ISSN du journal0950-9232
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Création12.10.2020 14:52:00
Première validation12.10.2020 14:52:00
Heure de mise à jour15.03.2023 22:49:48
Changement de statut15.03.2023 22:49:48
Dernière indexation17.01.2024 11:12:31
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