Cell-to-cell transmission of p53 aggregates: a novel player in oncology?

Naoyuki Iwahashi; Midori Ikezaki; Hiroyuki Saito; Kenji Uchimura; Kazuchika Nishitsuji

doi:10.1080/23723556.2021.1892444

Cell-to-cell transmission of p53 aggregates: a novel player in oncology?

Mol Cell Oncol. 2021 Mar 22;8(2):1892444. doi: 10.1080/23723556.2021.1892444. eCollection 2021.

Authors

Naoyuki Iwahashi¹, Midori Ikezaki², Hiroyuki Saito³, Kenji Uchimura⁴, Kazuchika Nishitsuji²

Affiliations

¹ Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.
² Department of Biochemistry, Wakayama Medical University, Wakayama, Japan.
³ Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
⁴ Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576 CNRS, Université de Lille, Villeneuve d'Ascq, France.

Abstract

The mutants of the tumor suppressor protein p53 form protein aggregates. It has been proposed that these aggregates propagate like prions, albeit the detailed mechanism of the propagation is unclear. Our recent study revealed that sulfated glycosaminoglycans, especially highly sulfated domains of heparan sulfate (heparan sulfate S-domains), participate in cancer pathology by mediating transcellular propagation of p53 aggregates.

Keywords: glycosaminoglycan; heparan sulfate; p53; prion; protein aggregates.

Grants and funding

This work was partly supported by Grants-in-Aid for Young Scientists [B-15K19488 and B-17K16123 to K.N.] and [JP18K16776 to N.I.] from the Japan Society for the Promotion of Science, and Grants-in-Aid from the the Japan Society for the Promotion of Science, and Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) [JP15K08265 and JP16KK0202 to K.U.]. This study was partially supported by an internal grant of Wakayama Medical University [Tokutei-kenkyu-zyosei 2019 and 2020].