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.

中文翻译：

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p53 淀粉样蛋白病理学与较高的癌症等级相关，无论突变型还是野生型形式。

p53（也称为 TP53）突变和淀粉样蛋白形成长期以来与癌症发病机制相关；然而，p53 淀粉样蛋白负荷与癌症进展之间的联系缺乏直接证明。使用多学科技术和 59 个组织（来自印度癌症个体的 53 个口腔和胃癌肿瘤组织样本和 6 个非癌症口腔和胃组织样本），我们发现 p53 淀粉样蛋白负荷和癌症分级高度相关。此外，下一代测序（NGS）数据表明，不仅突变型p53（例如单核苷酸变异、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蛋白在大多数癌组织中。有趣的是，在所有这些癌症组织中，p53 显示 DNA 结合和转录活性的丧失，这表明淀粉样蛋白负荷水平与丧失程度和癌症分级的增加相关。p53 淀粉样蛋白还在高级肿瘤组织中隔离更高量的相关 p63 和 p73（也分别称为 TP63 和 TP73）蛋白。数据表明p53错误折叠和/或聚集，以及随后的淀粉样蛋白形成，导致肿瘤抑制功能的丧失和致癌功能的获得，其恶化可能决定癌症等级。