Titre :

Impacts of cytoplasmic p53 aggregates on the prognosis and the transcriptome in lung squamous cell carcinoma

Auteur(s) :

Nishitsuji, Kazuchika [Auteur]
Mito, Remi [Auteur]
Ikezaki, Midori [Auteur]
Yano, Hiromu [Auteur]
Fujiwara, Yukio [Auteur]
Matsubara, Eri [Auteur]
Nishikawa, Taro [Auteur]
Ihara, Yoshito [Auteur]
Uchimura, Kenji [Auteur]
Iwahashi, Naoyuki [Auteur]
Sakagami, Takuro [Auteur]
Suzuki, Makoto [Auteur]
Komohara, Yoshihiro [Auteur]

Titre de la revue :

Cancer Science

Nom court de la revue :

Cancer Science

Numéro :

115

Pagination :

2947-2960

Éditeur :

Wiley

Date de publication :

2024-06-21

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

AbstractThe tumor suppressor TP53 gene, the most frequently mutated gene in human cancers, produces the product tumor protein p53, which plays an essential role in DNA damage. p53 protein mutations may contribute to ...
Lire la suite >AbstractThe tumor suppressor TP53 gene, the most frequently mutated gene in human cancers, produces the product tumor protein p53, which plays an essential role in DNA damage. p53 protein mutations may contribute to tumorigenesis by loss of tumor suppressive functions and malignancy of cancer cells via gain‐of‐oncogenic functions. We previously reported that mutant p53 proteins form aggregates and that cytoplasmic p53 aggregates were associated with poor prognosis in human ovarian cancer. However, the prognostic impact of p53 aggregation in other tumors including lung squamous cell carcinoma (SCC) is poorly understood. Here, we demonstrated that lung SCC cases with cytoplasmic p53 aggregates had a significantly poor clinical prognosis. Analysis via patient‐derived tumor organoids (PDOs) established from lung SCC patients and possessing cytoplasmic p53 aggregates showed that eliminating cytoplasmic p53 aggregates suppressed cell proliferation. RNA sequencing and transcriptome analysis of p53 aggregate‐harboring PDOs indicated multiple candidate pathways involved in p53 aggregate oncogenic functions. With lung SCC‐derived cell lines, we found that cytoplasmic p53 aggregates contributed to cisplatin resistance. This study thus shows that p53 aggregates are a predictor of poor prognosis in lung SCC and suggests that detecting p53 aggregates via p53 conventional immunohistochemical analysis may aid patient selection for platinum‐based therapy.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire

Date de dépôt :

2025-01-20T13:06:11Z