TIPE1 suppresses invasion and migration through down-regulating Wnt/β-catenin pathway in gastric cancer.
TIPE1 suppresses invasion and migration through down-regulating Wnt/β-catenin pathway in gastric cancer.
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TIPE1通过下调Wnt/β-catenin通路抑制胃癌侵袭和迁移
DOI：
10.1111/jcmm.13362
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Yi F
中科院分区：
文献类型：
--
作者：
Liu W;Chen Y;Xie H;Guo Y;Ren D;Li Y;Jing X;Li D;Wang X;Zhao M;Zhu T;Wang Z;Wei X;Gao F;Wang X;Liu S;Zhang Y;Yi F
上皮间质转化（EMT）在胃癌的侵袭和转移中起重要作用。因此，识别EMT的关键分子将为胃癌患者的治疗提供新的治疗策略。TIPE 1是TIPE（TNFAIP 8）家族的新成员，其对进展和转移的贡献尚未被评估。在本研究中，我们发现TIPE 1的水平显着降低，并与胃癌组织中的分化状态和远处转移呈负相关。我们进一步观察到TIPE 1在侵袭性胃癌细胞系中的过表达降低了它们在体外和体内的转移特性，如通过显著抑制裸鼠中胃癌细胞的EMT和转移所证明的。因此，TIPE 1在高分化胃癌细胞系（AGS）中的基因沉默抑制了这些过程。从机制上讲，我们发现TIPE 1介导的Wnt/β-catenin信号传导是将TIPE 1与EMT抑制联系起来的关键信号转导途径之一。重要的是，TIPE 1显著抑制了MMP 2和MMP 9的表达和活性，这两种蛋白被证明促进肿瘤进展并与EMT有关。这些研究结果为更好地了解TIPE 1在胃癌进展和转移中的生物学活性提供了新的证据，并表明TIPE 1可能是胃癌诊断和治疗的创新靶点。
Epithelial–mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well‐differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1‐medicated Wnt/β‐catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer.
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影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
TIPE2 是一种新型免疫调节剂，可预防实验性中风。
影响因子：
4.8
作者：
Zhang, Yan;Wei, Xinbing;Yi, Fan
通讯作者：
Yi, Fan
TIPE2，先天性和适应性免疫的负调节因子，可维持免疫稳态。
影响因子：
64.5
作者：
Sun, Honghong;Gong, Shunyou;Chen, Youhai H.
通讯作者：
Chen, Youhai H.
影响因子：
9
作者：
通讯作者：
--
影响因子：
51.1
作者：
Bray, Freddie;Jemal, Ahmedin;Forman, David
通讯作者：
Forman, David