title: Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma.
abstract: Germinal center lymphoma is a heterogeneous human lymphoma entity. Here we report that constitutive activity of SHP2 (PTPN11) and its downstream kinase ERK is essential for the viability of germinal center lymphoma cells and disease progression. Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma. Furthermore, SHP2/ERK signaling is required to maintain the CD19/c-Myc loop, which preferentially promotes survival of a distinct subtype of germinal center lymphoma cells carrying the MYC/IGH translocation. These findings demonstrate a critical function for SHP2/ERK signaling upstream of c-Myc in germinal center lymphoma cells and provide a rationale for targeting SHP2 in the therapy of germinal center lymphoma.
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Zhejiang Province People's Hospital, Hangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Nephrology, Zhejiang Province People's Hospital, Hangzhou, China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Basic Medical College, Capital Medical University, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Central Laboratory, Epitomics (Hangzhou) Biotech Co. Ltd, Hangzhou, Zhejiang, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, MA, USA.
authors.forename: Wande
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yuehai
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China zhouren@zju.edu.cn.
authors.forename: Ren
authors.initials: R
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D047468:Immunoprecipitation; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D007143:Immunoglobulin Heavy Chains; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11