Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.
Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.
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Intelectin 1 可抑制肿瘤进展，并与提高胃癌的生存率相关。
DOI：
10.18632/oncotarget.3753
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发表时间：
2015-06-30
期刊：
影响因子：
--
通讯作者：
Tong Q
中科院分区：
文献类型：
--
作者：
Li D;Zhao X;Xiao Y;Mei H;Pu J;Xiang X;Jiao W;Song H;Qu H;Huang K;Zheng L;Tong Q
最近的证据表明，智力素1 (ITLN1)，一种分泌性凝集素，在人类癌症中的新作用。我们之前的研究已经暗示了ITLN1在胃癌侵袭性中的潜在作用。在此，我们探讨了ITLN1在胃癌进展中的功能、下游靶点及其临床意义。我们证明了ITLN1增加了肝细胞核因子4α (HNF4α)的水平，从而抑制了胃癌细胞中β-catenin的核易位和转录活性。从机制上讲，ITLN1通过灭活磷酸肌苷3-激酶/AKT/Ikappa B激酶信号通路，降低了胃癌细胞中抑制HNF4α表达的转录因子核因子-kappa B的活性。功能增益和功能丧失研究表明，ITLN1在体外和体内抑制胃癌细胞的生长、侵袭和转移。此外，恢复HNF4α的表达可以阻止itln1介导的胃癌细胞这些生物学特性的变化。在临床胃癌组织中，HNF4α的表达与ITLN1的表达呈正相关。ITLN1或HNF4α高表达的患者生存率更高。综上所述，这些数据表明ITLN1通过上调HNF4α抑制胃癌的进展，并与胃癌患者的生存率提高有关。
Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory lectin, in human cancers. Our previous studies have implicated the potential roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated the functions, downstream targets, and clinical significance of ITLN1 in the progression of gastric cancer. We demonstrated that ITLN1 increased the levels of hepatocyte nuclear factor 4 alpha (HNF4α), resulting in suppression of nuclear translocation and transcriptional activity of β-catenin in gastric cancer cells. Mechanistically, ITLN1 attenuated the activity of nuclear factor-kappa B, a transcription factor repressing the HNF4α expression, in gastric cancer cells through inactivating the phosphoinositide 3-kinase/AKT/Ikappa B kinase signaling. Gain- and loss-of-function studies demonstrated that ITLN1 suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. In addition, restoration of HNF4α expression prevented the gastric cancer cells from ITLN1-mediated changes in these biological features. In clinical gastric cancer tissues, HNF4α expression was positively correlated with that of ITLN1. Patients with high ITLN1 or HNF4α expression had greater survival probability. Taken together, these data indicate that ITLN1 suppresses the progression of gastric cancer through up-regulation of HNF4α, and is associated with improved survival in patients with gastric cancer.