p53突变和淀粉样形成与癌症发生机制长期相关，然而，直接证明p53淀粉负载与癌症进展之间的联系仍然缺乏。利用多学科技术和一个包含59例肿瘤组织（其中53例来自印度癌症患者，6例来自正常组织）的队列研究口腔和胃癌类型，我们展示了p53淀粉负载与癌症分级之间存在高度相关性。此外，下一代测序（NGS）数据显示，在大多数癌症组织中，不仅突变p53（例如，单核苷酸变异（SNVs），缺失和插入），而且野生型p53也在细胞核（50％）和/或细胞质中形成淀粉样。有趣的是，在所有这些癌症组织中，p53显示出失去DNA结合和转录活性，这在淀粉负载和癌症分级中非常严重。p53淀粉体还在高级别肿瘤组织中更多地螯合p63 / p73同工型。数据表明，p53的错折/聚集和随后的淀粉样形成导致p53的肿瘤发生功能的损失和获得，进一步加深了癌症分级。© 2023。由生物学家有限公司出版。

p53 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 a cohort of 59 tumor tissues (53 from Indian cancer patients and six normal tissues) of oral and stomach cancer types, we showed that p53 amyloid load and cancer grades are highly correlated. Further, next-generation sequencing (NGS) data suggest that not only mutant p53 (e.g., SNVs, 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, which is highly aggravated with the amyloid load and cancer grades. The p53 amyloids also sequester higher amounts of p63/p73 isoforms in higher-grade tumor tissues. The data suggest p53 misfolding/aggregation and subsequent amyloid formation lead to loss and gain of p53 tumorigenic function, aggravation of which might determine the cancer grades.© 2023. Published by The Company of Biologists Ltd.