A self-enforcing HOXA11/Stat3 feedback loop promotes stemness properties and peritoneal metastasis in gastric cancer cells
A self-enforcing HOXA11/Stat3 feedback loop promotes stemness properties and peritoneal metastasis in gastric cancer cells
复制标题
自我执行的 HOXA11/Stat3 反馈回路促进胃癌细胞的干性特性和腹膜转移
DOI：
10.7150/thno.36277
复制
发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Zhang, Jun
中科院分区：
文献类型：
--
作者：
Wang, Chao;Shi, Min;Zhang, Jun
理由：腹膜转移是胃癌患者最常见且危及生命的转移之一。播散形成腹膜转移的胃癌细胞表现出与邻近胃粘膜上皮细胞甚至原发胃癌细胞不同的多种特征。我们假设腹膜灶的基因表达谱可以揭示可能作为转移激活因子的基因的身份。方法：在本研究中，我们通过体外、体内、人、小鼠的硅癌和胃癌组织研究表明，homebox A11 （HOXA11）能有效促进胃癌细胞的腹膜转移。结果：其作用机制包括改变肿瘤干细胞，增强其粘附、迁移、侵袭能力和抗细胞凋亡能力。这主要是通过HOXA11与Stat3之间形成正反馈回路，参与Stat3信号通路的刺激实现的。结论：这些发现揭示了一种新的腹膜转移激活因子，并证明了HOXA11、Stat3与胃癌细胞的癌干性之间的关联，从而揭示了一种以前未被描述的腹膜转移机制。
Rationale: Peritoneal metastasis is one of the most common and life-threatening metastases in gastric cancer patients. The disseminated gastric cancer cells forming peritoneal metastasis exhibit a variety of characteristics that contrast with those of adjacent epithelial cell of gastric mucosa and even primary gastric cancer cells. We hypothesized that the gene expression profiles of peritoneal foci could reveal the identities of genes that might function as metastatic activator. Methods: In this study, we show, using in vitro, in vivo, in silico and gastric cancer tissues studies in humans and mice, that Homoebox A11 (HOXA11) potently promote peritoneal metastasis of gastric cancer cells. Results: Its mechanism of action involves alternation of cancer stemness and subsequently enhancement of the adhesion, migration and invasion and anti-apoptosis. This is achieved, mainly, through formation of a positive feedback loop between HOXA11 and Stat3, which is involved in the stimulation of Stat3 signaling pathway. Conclusions: These observations uncover a novel peritoneal metastatic activator and demonstrate the association between HOXA11, Stat3 and cancer stemness of gastric cancer cells, thereby revealing a previously undescribed mechanism of peritoneal metastasis.