Abstract
We conducted a study concerning the suppressive mechanism of KAI1/CD82 on hepatoma cell metastasis. Hepatocyte growth factor (HGF) induces the migration of hepatoma cells through activation of cellular sphingosine kinase 1 (SphK1). Adenovirus-mediated gene transfer of KAI1 (Ad-KAI1) downregulates the SphK1 expression and suppresses the HGF-induced migration of SMMC-7721 human hepatocellcular carcinoma cells. Overexpression of KAI1/CD82 significantly elevates Sprouty2 at the protein level. Ablation of Sprouty2 with RNA interference can block the KAI1/CD82-induced suppression of hepatoma cell migration and downregulation of SphK1 expression. It is demonstrated that KAI1/CD82 suppresses HGF-induced migration of hepatoma cells via upregulation of Sprouty2.
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Liu W M, Zhang X A. KAI1/CD82, a tumor metastasis suppressor. Cancer Lett, 2006, 240: 183–194, 16260083, 10.1016/j.canlet.2005.08.018, 1:CAS:528:DC%2BD28XntlGjtb0%3D
Jackson P, Marreiros A, Russell P J. KAI1 tetraspanin and metastasis suppressor. Int J Biochem Cell Biol, 2005, 37: 530–534, 15618009, 10.1016/j.biocel.2004.08.009, 1:CAS:528:DC%2BD2cXhtFGiu7rO
Guo X Z, Friess H, Graber H U, et al. KAI1 expression is up-regulated in early pancreatic cancer and decreased in the presence of metastases. Cancer Res, 1996, 56: 4876–4880, 8895737, 1:CAS:528:DyaK28XmsFygsbs%3D
Higashiyama M, Kodama K, Yokouchi H, et al. KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor: An immunohisto-chemical analysis. Cancer, 1998, 83: 466–474., 9690539, 10.1002/(SICI)1097-0142(19980801)83:3<466::AID-CNCR15>3.0.CO;2-U, 1:CAS:528:DyaK1cXlt1agtb8%3D
Guo X Z, Friess H, Di Mola F F, et al. KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma. Hepatology, 1998, 28: 1481–1488, 9828210, 10.1002/hep.510280606, 1:CAS:528:DyaK1cXotFSgsbg%3D
Muneyuki T, Watanabe M, Yamanaka M, et al. KAI1/CD82 expression as a prognosic factor in sporadic colorectal cancer. Anticancer Res, 2001, 21: 3581–3587, 11848527, 1:CAS:528:DC%2BD38XhvFGmsbY%3D
Bandyopadhyay S, Zhan R, Chaudhuri A, et al. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nat Med, 2006, 12: 933–938, 16862154, 10.1038/nm1444, 1:CAS:528:DC%2BD28Xnsl2iur0%3D
Iiizumi M, Bandyopadhyay S, Watabe K. Interaction of Duffy antigen receptor for chemokines and KAI1: A critical step in metastasis suppression. Cancer Res, 2007, 67: 1411–1414, 17308076, 10.1158/0008-5472.CAN-06-3801, 1:CAS:528:DC%2BD2sXhvVWrtbc%3D
Sridhar S C, Miranti C K. Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases. Oncogene, 2006, 25: 2367–2378, 16331263, 10.1038/sj.onc.1209269, 1:CAS:528:DC%2BD28XjsVWku7c%3D
Zhang X A, He B, Zhou B, et al. Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration. J Biol Chem, 2003, 278: 27319–27328, 12738793, 10.1074/jbc.M303039200, 1:CAS:528:DC%2BD3sXltlOjs78%3D
Odintsova E, Sugiura T, Berditchevski F. Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/ KAI-1. Curr Biol, 2000, 10: 1009–1012, 10985391, 10.1016/S0960-9822(00)00652-7, 1:CAS:528:DC%2BD3cXmtVGiu78%3D
Dikic I, Giordano S. Negative receptor signaling. Curr Opin Cell Biol, 2003, 15: 128–135, 12648667, 10.1016/S0955-0674(03)00004-8, 1:CAS:528:DC%2BD3sXitV2msrc%3D
Lo T L, Yusoff P, Fong C W, et al. The ras/mitogen-activated protein kinase pathway inhibitor and likely tumor suppressor proteins, Sprouty 1 and Sprouty 2 are deregulated in breast cancer. Cancer Res, 2004, 64: 6127–6136, 15342396, 10.1158/0008-5472.CAN-04-1207, 1:CAS:528:DC%2BD2cXntFClsb4%3D
McKie A B, Douglas D A, Olijslagers S, et al. Epigenetic inactivation of the human Sprouty2 (hSPRY2) homologue in prostate cancer. Oncogene, 2005, 24: 2166–2174, 15735753, 10.1038/sj.onc.1208371, 1:CAS:528:DC%2BD2MXisFejurg%3D
Fong C W, Chua M S, McKie A B, et al. Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma. Cancer Res, 2006, 66: 2048–2058, 16489004, 10.1158/0008-5472.CAN-05-1072, 1:CAS:528:DC%2BD28XhsFamu70%3D
Lee C C, Putnam A J, Miranti C K, et al. Overexpression of Sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene, 2004, 23: 5193–5202, 15122328, 10.1038/sj.onc.1207646, 1:CAS:528:DC%2BD2cXlt1Oksb8%3D
Cabrita M A, Jäggi F, Widjaja S P, et al. A functional interaction between Sprouty proteins and caveolin-1. J Biol Chem, 2006, 281: 29201–29212, 16877379, 10.1074/jbc.M603921200, 1:CAS:528:DC%2BD28XpvFamsL4%3D
Xia P, Wang L, Gamble J R, et al. Activation of sphingosine kinase by tumor necrosis factor-alpha inhibits apoptosis in human endothelial cells. J Biol Chem, 1999, 274: 34499–34505, 10567432, 10.1074/jbc.274.48.34499, 1:CAS:528:DyaK1MXnslOkuro%3D
Duan H F, Qu C K, Zhang Q W, et al. Sphingosine kinase activation regulates hepatocyte growth factor induced migration of endothelial cells. Exp Cell Res, 2004, 298: 593–601, 15265705, 10.1016/j.yexcr.2004.04.049, 1:CAS:528:DC%2BD2cXlvVWht7c%3D
Jiang Y, Xu W, Lu J, et al. Invasiveness of hepatocellular carcinoma cell lines: Contribution of hepatocyte growth factor, c-met, and transcription factor Ets-1. Biochem Biophys Res Commun, 2001, 286: 1123–1130, 11527416, 10.1006/bbrc.2001.5521, 1:CAS:528:DC%2BD3MXmtlejurY%3D
Maceyka M, Payne S G, Milstien S, et al. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim Biophys Acta, 2002, 30: 193–201
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Supported by the National Natural Science Foundation of China (Grant Nos. 30670954 and 30670885)
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Mu, Z., Wang, H., Zhang, J. et al. KAI1/CD82 suppresses hepatocyte growth factor-induced migration of hepatoma cells via upregulation of Sprouty2. SCI CHINA SER C 51, 648–654 (2008). https://doi.org/10.1007/s11427-008-0086-1
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DOI: https://doi.org/10.1007/s11427-008-0086-1