机构：[1]Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.[2]Department of Neuropathology, Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.[3]Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.[4]Sichuan Lung Cancer Institute, Sichuan Lung Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院
Over-expression of Gli1 is very common in lung cancer. However, the underlying molecular mechanism remains largely unknown. Here, using mass spectrum, we have identified WW45 as a binding partner of Gli1. WW45 interacted with Gli1, promoted its ubiquitination and inhibited the expression of its target genes. In the functional studies, WW45 inhibited the growth and migration of lung cancer cells. Knocking down the expression of WW45 promoted the growth and migration of lung cancer cells, which was rescued by down-regulation of Gli1. Moreover, over-expression of WW45 inhibited the tumorigenesis in a de novo lung cancer tumorigenesis mouse model (LKB-Ras) as well as the expression of Gli1. Also over-expression of WW45 improved the survival of these mice. In addition, the expression of WW45 was down-regulated in the clinical lung cancer samples, which was inversely correlated with the expression of Gli1. Taken together, this study demonstrated the suppressive roles of WW45 in lung cancer by inhibiting the Hedgehog/Gli1 signaling.
基金：
National Natural Science Foundation of China (No.81572288, to Qinghua Zhou; No.81302002, to Xuebing Li; No.81502166, to Xuexia Zhou), the Foundation of Tianjin Medical University General Hospital (No. ZYYFY2014038, to Xuexia Zhou), the Tianjin Natural Science Foundation (No. 14JCQNJC12300, to Xuebing Li) and the “New Century” Talent Training Project of Tianjin Medical University General Hospital (2014, to Xuebing Li).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|1 区医学
小类|2 区细胞生物学2 区肿瘤学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
通讯作者：
通讯机构：[1]Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.[4]Sichuan Lung Cancer Institute, Sichuan Lung Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714)：
Li Xuebing,Zhou Xuexia,Fan Yaguang,et al.WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer.[J].Oncotarget.2016,7(42):68966-68975.doi:10.18632/oncotarget.12155.
APA：
Li Xuebing,Zhou Xuexia,Fan Yaguang,Zhang Yalong,Zu Lingling...&Zhou Qinghua.(2016).WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer..Oncotarget,7,(42)
MLA：
Li Xuebing,et al."WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer.".Oncotarget 7..42(2016):68966-68975
医学