TY - JOUR
T1 - Arl13b promotes gastric tumorigenesis by regulating Smo trafficking and activation of the hedgehog signaling pathway
AU - Shao, Jia
AU - Xu, Linlin
AU - Chen, Limin
AU - Lu, Quqin
AU - Xie, Xinsheng
AU - Shi, Wei
AU - Xiong, Huanting
AU - Shi, Chao
AU - Huang, Xuan
AU - Mei, Jinhong
AU - Rao, Hai
AU - Lu, Hua
AU - Lu, Nonghua
AU - Luo, Shiwen
N1 - Funding Information:
We are grateful to Dr. Cheng Luo, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, for technical assistance of protein purification. This work was supported in part by grants from the National Natural Science Foundation of China (31171359 and 31460305 to S. Luo; 81460376 to L. Xu). H. Lu was supported in part by NIH-NCI grants R01CA095441 and R01CA172468. H. Rao was supported by grant R01GM118350 from the NIH. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-16-2461
DO - 10.1158/0008-5472.CAN-16-2461
M3 - Article
C2 - 28611043
AN - SCOPUS:85026742723
VL - 77
SP - 4000
EP - 4013
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 15
ER -