Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室

	Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells
	Zhou YQ 1; Xiong LP 1; Xu GQ[*]1,3; Zhang Y 1; Yu R 2; Jiang XG 1
刊名	JOURNAL OF PROTEOMICS
	2016
卷号	148 期号:X 页码:94-104
关键词	ADAM12 E-cadherin Label-free Myoferlin Quantitative proteomics Spectral counting
通讯作者	gux2002@suda.edu.cn
合作状况	其它
英文摘要	A Disintegrin and Metalloproteinase 12 (ADAM12) is expressed significantly higher in multiple tumors than in normal tissues and has been used as a prognostic marker for the evaluation of cancer progression. Although several ADAM12 substrates have been identified biochemically and its proteolytic function has been explored, the upstream regulators and the interacting proteins have not been systematically investigated. Here, we use immunoprecipitation and mass spectrometry (MS)-based quantitative proteomic approaches to identify 28 interacting partners for the long form of ADAM12 (ADAM12-L) in HeLa cells. Proteins that regulate cell proliferation, invasion, and epithelial to mesenchymal transition are among the identified ADAM12-interacting proteins. Further biochemical experiments discover that the protein level and the stability of ADAM12 are upregulated by one of its interacting proteins, myoferlin. In addition, myoferlin also increases the proteolytic activity of ADAM12, leading to the reduction of an ADAM12 substrate, E-cadherin. This result implies that ADAM12 and its interacting proteins might converge to certain signaling pathways in the regulation of cancer cell progression. The information obtained here might be useful in the development of new strategies for modulating cell proliferation and invasion involved in the regulation between ADAM12 and its interacting partners. MS data are available via ProteomeXchange with identifier PXD003560. Biological significance: Regulation of the proliferation and invasion of cancer cells is important in cancer treatment. ADAM12 has been found to play important roles in regulating these processes and identification of its interacting partners will improve our understanding of its biological functions and provide basis for functional modulation. Through mass spectrometry-based quantitative proteomic approaches, we identify the interacting partners for ADAM12 in a human cancer cell line and find many proteins that are involved in the proliferation and invasion of cancer cells. A novel regulator, myoferlin, of ADAM12 is discovered and this protein increases ADAM12 expression level, stability, and its enzymatic activity, leading to the reduction of its substrate, E-cadherin, which plays important roles in the regulation of cell adhesion and tumor metastasis. This result provides a connection for two highly expressed proteins in cancer cells and may shed light on the regulation of their biological functions in cancer progression.
收录类别	SCI
资助信息	This work was supported by the National Natural Science Foundation of China (31470772), National Basic Research Program of China (973 Program, 2012CB947602), Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases (BM2013003), a project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10639]
专题	昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Jiangsu Key Laboratory ofTranslational Research and Therapy for Neuro-Psycho-Diseases& CollegeofPharmaceuticalSciences,JiangsuKeyLaboratory ofPreventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China 2.Department of Oncology, Suzhou Municipal Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215002, China 3.Joint Laboratory of Animal Models for Human Diseases and Drug Development, Soochow University and Kunming Institute of Zoology, Chinese Academy of Sciences, China
推荐引用方式 GB/T 7714	Zhou YQ,Xiong LP,Xu GQ[*],et al. Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells[J]. JOURNAL OF PROTEOMICS,2016,148(X):94-104.
APA	Zhou YQ,Xiong LP,Xu GQ[*],Zhang Y,Yu R,&Jiang XG.(2016).Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells.JOURNAL OF PROTEOMICS,148(X),94-104.
MLA	Zhou YQ,et al."Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells".JOURNAL OF PROTEOMICS 148.X(2016):94-104.