细胞生长
细胞生物学
信号转导
梅林(蛋白质)
莫辛
细胞周期
抑制器
雅普1
蛋白激酶B
癌基因
PI3K/AKT/mTOR通路
磷酸化
放射毒素
基因敲除
抑癌基因
细胞
下调和上调
癌症
激酶
作者
Yang Li,Min Liu,Shuting Yang,Ashley M. Fuller,T.S. Karin Eisinger-Mathason,Shuting Yang
出处
期刊:Oncogene
[Springer Nature]
日期:2021-03-08
卷期号:40 (14): 2553-2566
被引量:15
标识
DOI:10.1038/s41388-020-01599-z
摘要
Osteosarcoma (OS) is the most common primary malignancy of the bone that predominantly affects children and adolescents. Hippo pathway is a crucial regulator of organ size and tumorigenesis. However, how Hippo pathway regulates the occurrence of osteosarcoma is largely unknown. Here, we reported the regulator of G protein signaling protein 12 (RGS12) is a novel Hippo pathway regulator and tumor suppressor of osteosarcoma. Depletion of Rgs12 promotes osteosarcoma progression and lung metastasis in an orthotopic xenograft mouse model. Our data showed that the knockdown of RGS12 upregulates Ezrin expression through promoting the GNA12/13-RhoA-YAP pathway. Moreover, RGS12 negatively regulates the transcriptional activity of YAP/TEAD1 complex through its PDZ domain function to inhibit the expression and function of the osteosarcoma marker Ezrin. PDZ domain peptides of RGS12 can inhibit the development of intratibial tumor and lung metastases. Collectively, this study identifies that the RGS12 is a novel tumor suppressor in osteosarcoma through inhibiting YAP-TEAD1-Ezrin signaling pathway and provides a proof of principle that targeting RGS12 may be a therapeutic strategy for osteosarcoma.
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