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

Sengupta, S and Singh, N and Paul, A and Datta, D and Chatterjee, D and Mukherjee, S and Gadhe, L and Devi, J and Mahesh, Y and Jolly, MK and Maji, SK (2023) p53 amyloid pathology is correlated with higher cancer grade irrespective of the mutant or wild-type form. In: Journal of Cell Science, 136 (17).

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Official URL: https://doi.org/10.1242/jcs.261017


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. © 2023. Published by The Company of Biologists Ltd.

Item Type: Journal Article
Publication: Journal of Cell Science
Publisher: Company of Biologists Ltd
Additional Information: The copyright for this article belongs to the Authors.
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 01 Dec 2023 10:24
Last Modified: 01 Dec 2023 10:24
URI: https://eprints.iisc.ac.in/id/eprint/83424

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