机构:[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17 Section 3, People’s South Road, Chengdu 610041, People’s Republic of China.[2]Department of Urinary Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China.[3]Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, People’s Republic of China.
Aberrant expression of Na+/K+-ATPase α1 subunit (ATP1A1) is widely observed in multiple types of tumors, and its tissue-specific expression relates to cancer development. However, the functions and molecular mechanisms in renal cell carcinoma (RCC) are not fully understood.
We investigated the ATP1A1 expression changes and possible roles in RCC through a quantitative proteomic approach and an integrative biochemical assessment. We detected ATP1A1 in RCC with LC-MS/MS, and further validated its expression with immunohistochemical analyses of 80 pairs of the RCC tumor and non-tumor tissues samples. The association of ATP1A1 expression with RCC pathology was statistically analyzed. Cell proliferation, migration and apoptosis were measured by CCK-8, boyden chamber assay and flow cytometry, respectively. The production of reactive oxygen species (ROS) was labeled with a single staining using a commercial kit, and was further detected with flow cytometry.
The ATP1A1 shows a significantly decreased expression in human RCC tissues than in the adjacent non-tumor tissues. The RCC patients with ATP1A1-positive expression exhibit longer overall survival time than the ATP1A1-negative patients. The exogenous overexpression of ATP1A1 inhibits RCC cell proliferation and cell migration by increasing the production of ROS. In addition, ATP1A1-mediated Raf/MEK/ERK signaling pathway is suppressed in RCC cells, indicating the possible occurrence of induced cell apoptosis.
Our in vitro and in vivo data of ATP1A1 inhibitory roles in RCC progression suggest that ATP1A1 is a potential novel suppressor protein for renal cancer.
基金:
National 863 High Tech FoundationNational High Technology Research and Development Program of China [2014AA020608]; National Key Basic Research Program of ChinaNational Basic Research Program of China [2013CB911303, 2011CB910703]; National Natural Sciences Foundation of ChinaNational Natural Science Foundation of China [31470810, 31071235, 30970654]; Science & Technology Department of Sichuan Province [2017JY0232]
语种:
外文
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|2 区医学
小类|3 区生化研究方法
最新[2023]版:
大类|3 区医学
小类|2 区生化研究方法
第一作者:
第一作者机构:[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17 Section 3, People’s South Road, Chengdu 610041, People’s Republic of China.
共同第一作者:
通讯作者:
通讯机构:[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17 Section 3, People’s South Road, Chengdu 610041, People’s Republic of China.
推荐引用方式(GB/T 7714):
Dan Zhang,Peng Zhang,Pengbo Yang,et al.Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma.[J].Clinical proteomics.2017,14(1):15.doi:10.1186/s12014-017-9150-4.
APA:
Dan Zhang,Peng Zhang,Pengbo Yang,Yu He,Xixi Wang...&Shufang Liang.(2017).Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma..Clinical proteomics,14,(1)
MLA:
Dan Zhang,et al."Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma.".Clinical proteomics 14..1(2017):15