MRC Toxicology Unit, Lancaster Road, Leicester, LE1 9HN, UK.
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Nat Commun. 2018 Aug 3;9(1):3070. doi: 10.1038/s41467-018-05368-1.
Cell-in-cell (CIC) structures are commonly seen in tumours. Their biological significance remains unclear, although they have been associated with more aggressive tumours. Here we report that mutant p53 promotes CIC via live cell engulfment. Engulfed cells physically interfere in cell divisions of host cells and for cells without p53 this leads to host cell death. In contrast, mutant p53 host cells survive, display aberrant divisions, multinucleation and tripolar mitoses. In xenograft studies, CIC-rich p53 mutant/null co-cultures show enhanced tumour growth. Furthermore, our results show that CIC is common within lung adenocarcinomas, is an independent predictor of poor outcome and disease recurrence, is associated with mutant p53 expression and correlated to measures of heterogeneity and genomic instability. These findings suggest that pro-tumorigenic entotic engulfment activity is associated with mutant p53 expression, and the two combined are a key factor in genomic instability.
细胞中包含细胞（CIC）结构在肿瘤中很常见。尽管它们与更具侵袭性的肿瘤有关，但它们的生物学意义尚不清楚。在这里，我们报告突变型 p53 通过活细胞吞噬作用促进 CIC。被吞噬的细胞会在物理上干扰宿主细胞的细胞分裂，而对于没有 p53 的细胞，这会导致宿主细胞死亡。相比之下，突变型 p53 宿主细胞存活下来，表现出异常分裂、多核化和三极有丝分裂。在异种移植研究中，富含 CIC 的 p53 突变体/缺失共培养显示出增强的肿瘤生长。此外，我们的结果表明，CIC 在肺腺癌中很常见，是预后不良和疾病复发的独立预测因子，与突变型 p53 表达相关，并与异质性和基因组不稳定性的衡量标准相关。这些发现表明，促肿瘤发生的胞噬性吞噬作用与突变型 p53 表达有关，两者的结合是基因组不稳定性的关键因素。
