机构：[1]Department of Biological Sciences, University of Delaware, Newark, Delaware, USA[2]Department of Biology, WestVirginia University, Morgantown, West Virginia, USA[3]Pittsburgh Heart, Lung and Blood Vascular Medicine Institute andDepartment of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA[4]State Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China[5]Department of Clinical Laboratory,The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming, China[6]Departmentof Biochemistry and Cancer Institute, West Virginia University School of Medicine, Morgantown, West Virginia, USA
Ephrin-B signaling has been implicated in many normal and pathological processes, including neural crest development and tumor metastasis. We showed previously that proteolysis of ephrin-B ligands by the disintegrin metalloprotease ADAM13 is necessary for canonical Wnt signal activation and neural crest induction in Xenopus, but it was unclear if these mechanisms are conserved in mammals. Here, we report that mammalian ADAM9 cleaves ephrin-B1 and ephrin-B2 and can substitute for Xenopus ADAM13 to induce the neural crest. We found that ADAM9 expression is elevated in human colorectal cancer (CRC) tissues and that knockdown (KD) of ADAM9 inhibits the migration and invasion of SW620 and HCT116 CRC cells by reducing the activity of Akt kinase, which is antagonized by ephrin-Bs. Akt is a signaling node that activates multiple downstream pathways, including the Wnt and mTOR pathways, both of which can promote CRC cell migration/invasion. Surprisingly, we also found that KD of ADAM9 downregulates Wnt signaling but has negligible effects on mTOR signaling in SW620 cells; in contrast, mTOR activity is suppressed while Wnt signaling remains unaffected by ADAM9 KD in HCT116 cells. These results suggest that mammalian ADAM9 cleaves ephrin-Bs to derepress Akt and promote CRC migration and invasion; however, the signaling pathways regulators.
基金：
National Institutes of Health [R01 GM114105, R01 DE029802, P20 GM104316, U54 GM104941, R35 GM133560]
第一作者机构：[1]Department of Biological Sciences, University of Delaware, Newark, Delaware, USA
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通讯作者：
推荐引用方式(GB/T 7714)：
Pathirennehelage Chandrasekera,Mark Perfetto,Congyu Lu,et al.Metalloprotease ADAM9 cleaves ephrin-B ligands and differentially regulates Wnt and mTOR signaling downstream of Akt kinase in colorectal cancer cells[J].JOURNAL OF BIOLOGICAL CHEMISTRY.2022,298(8):doi:10.1016/j.jbc.2022.102225.
APA：
Pathirennehelage Chandrasekera,Mark Perfetto,Congyu Lu,Minghui Zhuo,Harinath Bahudhanapati...&Shuo Wei.(2022).Metalloprotease ADAM9 cleaves ephrin-B ligands and differentially regulates Wnt and mTOR signaling downstream of Akt kinase in colorectal cancer cells.JOURNAL OF BIOLOGICAL CHEMISTRY,298,(8)
MLA：
Pathirennehelage Chandrasekera,et al."Metalloprotease ADAM9 cleaves ephrin-B ligands and differentially regulates Wnt and mTOR signaling downstream of Akt kinase in colorectal cancer cells".JOURNAL OF BIOLOGICAL CHEMISTRY 298..8(2022)
生物学