Details

Autor(en) / Beteiligte

• Soragni, Alice
• Janzen, Deanna M.
• Johnson, Lisa M.
• Lindgren, Anne G.
• Thai-Quynh Nguyen, Anh
• Tiourin, Ekaterina
• Soriaga, Angela B.
• Lu, Jing
• Jiang, Lin
• Faull, Kym F.
• Pellegrini, Matteo
• Memarzadeh, Sanaz
• Eisenberg, David S.

Titel

A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas

Ist Teil von

• Cancer cell, 2016-01, Vol.29 (1), p.90-103

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. [Display omitted] •We designed the peptide ReACp53 to halt aggregation of p53 in cells•ReACp53 rescues p53 transcription of target genes and restores apoptosis•In vivo ReACp53 halts progression and shrinks tumors bearing aggregation-prone p53•p53 aggregation in cancer is a target for therapy with ReACp53 as a lead compound Using p53-mutant, high-grade, serous ovarian carcinoma as model systems, Soragni et al. show that a cell-penetrating peptide designed to inhibit p53 amyloid formation rescues p53 functions and reduces in vivo xenograft growth and metastasis.