Arl13b Promotes Gastric Tumorigenesis by Regulating Smo Trafficking and Activation of the Hedgehog Signaling Pathway.
Arl13b Promotes Gastric Tumorigenesis by Regulating Smo Trafficking and Activation of the Hedgehog Signaling Pathway.
复制标题
Arl13b 通过调节 Smo 运输和 Hedgehog 信号通路激活促进胃肿瘤发生
DOI：
10.1158/0008-5472.can-16-2461
复制
发表时间：
2017-08-01
期刊：
影响因子：
11.2
通讯作者：
Luo S
中科院分区：
文献类型：
--
作者：
Shao J;Xu L;Chen L;Lu Q;Xie X;Shi W;Xiong H;Shi C;Huang X;Mei J;Rao H;Lu H;Lu N;Luo S
Hedgehog (Hh) 通路转导器 Smoothened (Smo) 的抑制剂已被批准用于癌症治疗，但 Smo 突变通常会导致肿瘤耐药，并且尚不清楚 Smo 是如何调节的。在这项研究中，我们确定了小 GTPase Arl13b 作为 Smo 的新伙伴和调节剂。 Arl13b 调节 Smo 稳定性、运输和定位，这对于 Hh 信号传导至关重要。在胃癌细胞中，Arl13b 在体外和体内刺激增殖、迁移和侵袭。在胃癌临床标本中，Arl13b 表达与肿瘤大小和浸润深度密切相关； Arl13b水平高的患者预后较差。我们的结果显示了 Arl13b 如何参与胃癌中 Hh 通路的激活。
Inhibitors of the Hedgehog (Hh) pathway transducer Smoothened (Smo) have been approved for cancer treatment, but Smo mutations often lead to tumor resistance and it remains unclear how Smo is regulated. In this study, we identified the small GTPase Arl13b as a novel partner and regulator of Smo. Arl13b regulated Smo stability, trafficking and localization which are each crucial for Hh signaling. In gastric cancer cells, Arl13b stimulated proliferation, migration and invasion in vitro and in vivo. In clinical specimens of gastric cancer, Arl13b expression correlated strongly with tumor size and depth of invasion; patients with high levels of Arl13b had a poor prognosis. Our results show how Arl13b participates in Hh pathway activation in gastric cancer.