{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:07:07Z","timestamp":1790006827187,"version":"4.0.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5448,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The Akt\/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt\/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt\/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt\/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2000.17738","type":"journal-article","created":{"date-parts":[[2003,12,31]],"date-time":"2003-12-31T12:34:56Z","timestamp":1072874096000},"page":"796-802","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":100,"title":["Hepatocyte growth factor promotes cell survival from Fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression"],"prefix":"10.1097","volume":"32","author":[{"given":"Atsushi","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Hayashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushi","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Shiraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2000.17738-BIB1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0074-7696(08)62312-8","volume":"68","author":"Wyllie","year":"1980","journal-title":"Int Rev Cytol"},{"key":"10.1053\/jhep.2000.17738-BIB2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0092-8674(00)81874-7","volume":"88","author":"Nagata","year":"1997","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB3","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1126\/science.7533326","volume":"267","author":"Nagata","year":"1995","journal-title":"Science"},{"key":"10.1053\/jhep.2000.17738-BIB4","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0092-8674(00)81334-3","volume":"87","author":"Alnemri","year":"1996","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB5","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/380723a0","volume":"380","author":"Enari","year":"1996","journal-title":"Nature"},{"key":"10.1053\/jhep.2000.17738-BIB6","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.278.5338.687","volume":"278","author":"Peso","year":"1997","journal-title":"Science"},{"key":"10.1053\/jhep.2000.17738-BIB7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1101\/gad.11.6.701","volume":"11","author":"Kennedy","year":"1997","journal-title":"Genes Dev"},{"key":"10.1053\/jhep.2000.17738-BIB8","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1073\/pnas.94.8.3627","volume":"94","author":"Ahmed","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2000.17738-BIB9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0092-8674(00)80405-5","volume":"91","author":"Datta","year":"1997","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB10","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.282.5392.1318","volume":"282","author":"Cardone","year":"1998","journal-title":"Science"},{"key":"10.1053\/jhep.2000.17738-BIB11","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB12","first-page":"624","volume":"277","author":"Liu","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1053\/jhep.2000.17738-BIB13","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1101\/gad.13.22.2905","volume":"13","author":"Datta","year":"1999","journal-title":"Genes Dev"},{"key":"10.1053\/jhep.2000.17738-BIB14","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1038\/sj.onc.1202393","volume":"17","author":"Rohn","year":"1998","journal-title":"Oncogene"},{"key":"10.1053\/jhep.2000.17738-BIB15","doi-asserted-by":"crossref","first-page":"6541","DOI":"10.1002\/j.1460-2075.1996.tb01045.x","volume":"15","author":"Alessi","year":"1996","journal-title":"EMBO J"},{"key":"10.1053\/jhep.2000.17738-BIB16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0092-8674(00)81780-8","volume":"95","author":"Stambolic","year":"1998","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB17","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1073\/pnas.96.11.6199","volume":"96","author":"Sun","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2000.17738-BIB18","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1073\/pnas.96.8.4240","volume":"96","author":"Cantley","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2000.17738-BIB19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/342440a0","volume":"342","author":"Nakamura","year":"1989","journal-title":"Nature"},{"key":"10.1053\/jhep.2000.17738-BIB20","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/hep.510300149","volume":"30","author":"Tsubouchi","year":"1999","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2000.17738-BIB21","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1084\/jem.184.5.2067","volume":"184","author":"Rodriguez","year":"1996","journal-title":"J Exp Med"},{"key":"10.1053\/jhep.2000.17738-BIB22","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3181\/00379727-217-44256","volume":"217","author":"Suzuki","year":"1998","journal-title":"Pro Soc Exp Biol Med"},{"key":"10.1053\/jhep.2000.17738-BIB23","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1006\/bbrc.1998.8293","volume":"244","author":"Kosai","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1053\/jhep.2000.17738-BIB24","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/5593","volume":"5","author":"Ueki","year":"1999","journal-title":"Nat Med"},{"key":"10.1053\/jhep.2000.17738-BIB25","first-page":"1513","volume":"7","author":"Sakata","year":"1996","journal-title":"Cell Growth Differ"},{"key":"10.1053\/jhep.2000.17738-BIB26","doi-asserted-by":"crossref","first-page":"9577","DOI":"10.1073\/pnas.93.18.9577","volume":"93","author":"Santoni-Rugiu","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2000.17738-BIB27","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1128\/MCB.19.5.3842","volume":"19","author":"Suzuki","year":"1999","journal-title":"Mol Cell Biol"},{"key":"10.1053\/jhep.2000.17738-BIB28","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1084\/jem.169.5.1747","volume":"169","author":"Yonehara","year":"1989","journal-title":"J Exp Med"},{"key":"10.1053\/jhep.2000.17738-BIB29","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1002\/j.1460-2075.1995.tb00245.x","volume":"14","author":"Kischkel","year":"1995","journal-title":"EMBO J"},{"key":"10.1053\/jhep.2000.17738-BIB30","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1046\/j.1365-2613.1998.730403.x","volume":"79","author":"Shiota","year":"1998","journal-title":"Int J Exp Pathol"},{"key":"10.1053\/jhep.2000.17738-BIB31","author":"Hayashida","year":"2000","unstructured":", , , . Cell death induction by CTL: Perforin\/Granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma. Proc Soc Exp Biol Med 2000; in press."},{"key":"10.1053\/jhep.2000.17738-BIB32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0092-8674(95)90405-0","volume":"80","author":"Hunter","year":"1995","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB33","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1083\/jcb.148.3.557","volume":"148","author":"Kazama","year":"2000","journal-title":"J Cell Biol"},{"key":"10.1053\/jhep.2000.17738-BIB34","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1054\/bjoc.1999.1016","volume":"82","author":"Ueoka","year":"2000","journal-title":"Br J Cancer"},{"key":"10.1053\/jhep.2000.17738-BIB35","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/(SICI)1097-4547(20000215)59:4<489::AID-JNR3>3.0.CO;2-9","volume":"59","author":"Zhang","year":"2000","journal-title":"J Neurosci Res"},{"key":"10.1053\/jhep.2000.17738-BIB36","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1096\/fasebj.13.15.2186","volume":"13","author":"Jones","year":"1999","journal-title":"FASEB J"},{"key":"10.1053\/jhep.2000.17738-BIB37","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1073\/pnas.96.1.145","volume":"96","author":"Kanuka","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2000.17738-BIB38","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1021\/bi00316a032","volume":"23","author":"Hidaka","year":"1984","journal-title":"Biochemistry"},{"key":"10.1053\/jhep.2000.17738-BIB39","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/S0021-9258(18)45857-7","volume":"267","author":"Nakanishi","year":"1992","journal-title":"J Biol Chem"},{"key":"10.1053\/jhep.2000.17738-BIB40","doi-asserted-by":"crossref","first-page":"15771","DOI":"10.1016\/S0021-9258(18)98476-0","volume":"266","author":"Toullec","year":"1991","journal-title":"J Biol Chem"},{"key":"10.1053\/jhep.2000.17738-BIB41","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1126\/science.281.5381.1309","volume":"281","author":"Green","year":"1998","journal-title":"Science"},{"key":"10.1053\/jhep.2000.17738-BIB42","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1093\/emboj\/17.6.1675","volume":"17","author":"Scaffidi","year":"1998","journal-title":"EMBO J"},{"key":"10.1053\/jhep.2000.17738-BIB43","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0092-8674(95)90411-5","volume":"80","author":"Yang","year":"1995","journal-title":"Cell"},{"key":"10.1053\/jhep.2000.17738-BIB44","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3181\/00379727-221-44386","volume":"221","author":"Suzuki","year":"1999","journal-title":"Proc Soc Exp Biol Med"},{"key":"10.1053\/jhep.2000.17738-BIB45","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.4049\/jimmunol.152.4.1751","volume":"152","author":"Wong","year":"1994","journal-title":"J Immunol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2000.17738","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200010000-00016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:25:20Z","timestamp":1733052320000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200010000-00016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2000.17738","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2000,10]]}}}