Extracellular calumenin suppresses ERK1/2 signaling and cell migration   by protecting fibulin-1 from MMP-13-mediated proteolysis

doi:10.1038/onc.2014.52

CORC > 北京大学 > 生命科学学院

	Extracellular calumenin suppresses ERK1/2 signaling and cell migration by protecting fibulin-1 from MMP-13-mediated proteolysis
	Wang, Q. ; Shen, B. ; Chen, L. ; Zheng, P. ; Feng, H. ; Hao, Q. ; Liu, X. ; Liu, L. ; Xu, S. ; Chen, J. ; Teng, J.
刊名	oncogene
	2015
关键词	MATRIX METALLOPROTEINASE-13 HEPATOCELLULAR-CARCINOMA MOLECULAR-CLONING BREAST-CANCER PROTEIN EXPRESSION PROGRESSION FIBRONECTIN METASTASIS MECHANISM
DOI	10.1038/onc.2014.52
英文摘要	Extracellular proteins are vital for cell activities, such as cell migration. Calumenin is highly conserved among eukaryotes, but its functions are largely unclear. Here, we identify extracellular calumenin as a suppressor of cell migration and tumor metastasis. Calumenin binds to and stabilizes fibulin-1, leading to inactivation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling. We further identify the minimal functional domain of calumenin (amino acids 74-138 and 214-280). Depletion of calumenin induces fibulin-1-and phospho-ERK1/2 (pERK1/2)-dependent promotion of cell migration. Consistently, in hepatocellular and pancreatic carcinoma, both calumenin and fibulin-1 are downregulated. Furthermore, we show that matrix metalloproteinase13 (MMP-13) proteolyzes fibulin-1 and that calumenin protects fibulin-1 from cleavage by MMP-13. Calumenin, together with fibulin-1, also interacts with fibronectin and depends on both syndecan-4 and a5a1-integrin to suppress ERK1/2 signaling and inhibit cell migration. Thus, extracellular calumenin regulates fibulin-1 to have crucial roles in ERK1/2 signaling and cell migration.; Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity; SCI(E); 0; ARTICLE; chenjg@pku.edu.cn; junlinteng@pku.edu.cn; 8; 1006-1018; 34
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/386107]
专题	生命科学学院
推荐引用方式 GB/T 7714	Wang, Q.,Shen, B.,Chen, L.,et al. Extracellular calumenin suppresses ERK1/2 signaling and cell migration by protecting fibulin-1 from MMP-13-mediated proteolysis[J]. oncogene,2015.
APA	Wang, Q..,Shen, B..,Chen, L..,Zheng, P..,Feng, H..,...&Teng, J..(2015).Extracellular calumenin suppresses ERK1/2 signaling and cell migration by protecting fibulin-1 from MMP-13-mediated proteolysis.oncogene.
MLA	Wang, Q.,et al."Extracellular calumenin suppresses ERK1/2 signaling and cell migration by protecting fibulin-1 from MMP-13-mediated proteolysis".oncogene (2015).