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p53 amyloid pathology is correlated with higher cancer grade irrespective of the mutant or wild-type form.

Authors :
Sengupta S
Singh N
Paul A
Datta D
Chatterjee D
Mukherjee S
Gadhe L
Devi J
Mahesh Y
Jolly MK
Maji SK
Source :
Journal of cell science [J Cell Sci] 2023 Sep 01; Vol. 136 (17). Date of Electronic Publication: 2023 Sep 08.
Publication Year :
2023

Abstract

p53 (also known as TP53) mutation and amyloid formation are long associated with cancer pathogenesis; however, the direct demonstration of the link between p53 amyloid load and cancer progression is lacking. Using multi-disciplinary techniques and 59 tissues (53 oral and stomach cancer tumor tissue samples from Indian individuals with cancer and six non-cancer oral and stomach tissue samples), we showed that p53 amyloid load and cancer grades are highly correlated. Furthermore, next-generation sequencing (NGS) data suggest that not only mutant p53 (e.g. single-nucleotide variants, deletions, and insertions) but wild-type p53 also formed amyloids either in the nucleus (50%) and/or in the cytoplasm in most cancer tissues. Interestingly, in all these cancer tissues, p53 displays a loss of DNA-binding and transcriptional activities, suggesting that the level of amyloid load correlates with the degree of loss and an increase in cancer grades. The p53 amyloids also sequester higher amounts of the related p63 and p73 (also known as TP63 and TP73, respectively) protein in higher-grade tumor tissues. The data suggest p53 misfolding and/or aggregation, and subsequent amyloid formation, lead to loss of the tumor-suppressive function and the gain of oncogenic function, aggravation of which might determine the cancer grade.<br />Competing Interests: Competing interests The authors declare no competing or financial interests.<br /> (© 2023. Published by The Company of Biologists Ltd.)

Details

Language :
English
ISSN :
1477-9137
Volume :
136
Issue :
17
Database :
MEDLINE
Journal :
Journal of cell science
Publication Type :
Academic Journal
Accession number :
37622400
Full Text :
https://doi.org/10.1242/jcs.261017