P53 是所有癌症中突变最频繁的抑癌基因。在人类癌症中，p53 的特定残基发生高频率突变，这些突变被称为热点突变。突变体 p53 通过功能获得 (GOF) 机制促进肿瘤进展。然而，由于胃癌不同的热点突变，其生物学特性，特别是其转移潜力仍不清楚。在本研究中，我们研究了p53依赖的转移表型。本研究检查了野生型、突变型p53-R175H和突变型p53-R273H NUGC-4胃癌细胞体外和体内转移潜力的差异。与野生型和突变型p53-R273H细胞相比，NUGC-4-突变型-p53-R175H细胞在增殖、伤口愈合和侵袭测定中分别表现出显着的细胞增殖、愈合和侵袭能力。两种 NUGC-4-mutant-p53 细胞类型均表达上皮间质转化 (EMT) 相关蛋白。此外，与 NUGC-4-mutant-p53-R273H 细胞相比，NUGC-4-mutant-p53-R175H 细胞与细胞外基质的附着较少，且 EMT 相关蛋白的表达较高。关于腹膜播散模型，NUCG-4-突变-p53-R175H和NUCG-4-突变-p53-R273H细胞表现出比NUGC-4-空细胞更少形成播散结节。相比之下，NUCG3-mutant-p53-R175H 中的肝转移比其他细胞系更频繁且数量更多。我们的结果表明，p53 状态的差异，即使是热点突变位点，不仅影响肝转移的特征细胞以及胃癌的转移能力。版权所有 © 2023 国际抗癌研究所 (Dr. George J. Delinasios)，保留所有权利。

P53 is the most frequently mutated tumor suppressor gene among all cancers. In human cancers, specific residues of p53 are mutated at a high frequency, and those mutations are known as hotspot mutations. Mutant p53 promotes tumor progression through the gain-of-function (GOF) mechanism. However, its biological characteristics, especially its metastatic potential, owing to different hotspot mutations in gastric cancer remain unclear. In the present study, we investigated the p53-depended metastatic phenotype.This study examined the differences in the metastatic potential of wild-type, mutant-p53-R175H, and mutant-p53-R273H NUGC-4 gastric cancer cells in vitro and in vivo.NUGC-4-mutant-p53-R175H cells showed significant cell proliferation, healing and invasive abilities in proliferation, wound healing and invasion assay, respectively, compared to wild-type and mutant-p53-R273H cells. Both NUGC-4-mutant-p53 cell types expressed epithelial-mesenchymal transition (EMT)-related proteins. Furthermore, NUGC-4-mutant-p53-R175H cells showed less attachment to the extracellular matrix and greater expression of EMT-related proteins than NUGC-4-mutant-p53-R273H cells. Regarding the peritoneal dissemination model, NUCG-4-mutant-p53-R175H and NUCG-4-mutant-p53-R273H cells demonstrated less frequent formation of dissemination nodules than NUGC-4-empty cells. In contrast, liver metastases were more frequent and greater in number in NUCG3-mutant-p53-R175H than in the other cell lines.Our results suggest that differences in the p53 status, even in the hotspot mutation site, affect not only the characteristics of the cells but also the metastatic ability of gastric cancer.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.