title: Negative regulation of hepatocellular carcinoma cell growth by signal regulatory protein alpha1.
abstract: Signal regulatory protein (SIRP) alpha1 is a member of the SIRP family that undergoes tyrosine phosphorylation and binds SHP-2 tyrosine phosphatase in response to various mitogens. The expression levels of SIRPalpha1 were decreased in HCC tissues, compared with the matched normal tissues. Exogenous expression of wild type SIRPalpha1, but not of a mutant SIRPalpha1 lacking the tyrosine phosphorylation sites, in SIRPalpha1-negative Huh7 human HCC cells resulted in suppression of tumor cell growth both in vitro and in vivo. Treatment of Huh7 transfectants with EGF or HGF induced tyrosine phosphorylation of SIRPalpha1 and its association with SHP-2, which were accompanied by reduced ERK1 activation. Expression of SIRPalpha1 significantly suppressed activation of NF-kappaB and also sensitized Huh7 cells to TNFalpha or cisplatin-induced cell death. In addition, SIRPalpha1-transfected Huh7 cells displayed reduced cell migration and cell spreading in a fashion that was dependent on SIRPalpha1/SHP-2 complex formation. In conclusion, a negative regulatory effect of SIRPalpha1 on hepatocarcinogenesis is exerted, at least in part, through inhibition of ERK and NF-kappaB pathways.
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
authors.forename: He-Xin
authors.initials: HX
authors.lastname: Yan
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Li
authors.forename: Shu-Qin
authors.initials: SQ
authors.lastname: Liu
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Cao
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Qiu
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Shan
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Yan
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Wu
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Tan
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000943:Antigens, Differentiation / Q000032:analysis / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division; D002465:Cell Movement; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000473:pathology* / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis / Q000502:physiology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D039842:Neural Cell Adhesion Molecule L1; D011971:Receptors, Immunologic; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases