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Article: Synergistic effects of epidermal growth factor and hepatocyte growth factor on human ovarian cancer cell invasion and migration: Role of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase

TitleSynergistic effects of epidermal growth factor and hepatocyte growth factor on human ovarian cancer cell invasion and migration: Role of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase
Authors
Issue Date2007
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 2007, v. 148 n. 11, p. 5195-5208 How to Cite?
AbstractOvarian cancer is the primary cause of death from gynecological malignancies with a poor prognosis characterized by widespread peritoneal dissemination. However, mechanisms of invasion and metastasis in ovarian cancer remain poorly understood. Epidermal growth factor (EGF) and hepatocyte growth factor (HGF) are often both overexpressed and contribute to the growth of ovarian cancer by activating autocrine pathways. In the present study, we investigated the mechanisms of invasive activity of EGF, HGF, and their synergistic effects in human ovarian cancer cells. Here our data suggest that EGF and HGF may use unique and overlapping signaling cascades leading to the invasive phenotype. We revealed that HGF-mediated cell migration and invasion required the coordinate activation of the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2. Although EGF-dependent invasive phenotype appeared to have similar requirements for phosphatidylinositol 3-kinase, this growth factor used the alternative p38 MAPK pathway for cell invasion. A significant role of p38 MAPK was further supported by the observation that expression of dominant negative p38 MAPK likewise inhibited EGF-dependent invasiveness and cell motility. We also showed that EGF cooperated with HGF to promote a highly invasive phenotype via the increased secretion of matrix metalloproteinase (MMP)-9. The coincident induction of MMP-9 was functionally significant because inclusion of MMP-9 inhibitor or an anti-MMP-9 neutralizing antibody abolished EGF- and HGF-induced cellular invasion. These findings provide insights into the mechanism of the malignant progression of ovarian cancer. Copyright © 2007 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/179017
ISSN
2015 Impact Factor: 4.159
2015 SCImago Journal Rankings: 2.363
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhou, HYen_US
dc.contributor.authorPon, YLen_US
dc.contributor.authorWong, ASTen_US
dc.date.accessioned2012-12-19T09:51:26Z-
dc.date.available2012-12-19T09:51:26Z-
dc.date.issued2007en_US
dc.identifier.citationEndocrinology, 2007, v. 148 n. 11, p. 5195-5208en_US
dc.identifier.issn0013-7227en_US
dc.identifier.urihttp://hdl.handle.net/10722/179017-
dc.description.abstractOvarian cancer is the primary cause of death from gynecological malignancies with a poor prognosis characterized by widespread peritoneal dissemination. However, mechanisms of invasion and metastasis in ovarian cancer remain poorly understood. Epidermal growth factor (EGF) and hepatocyte growth factor (HGF) are often both overexpressed and contribute to the growth of ovarian cancer by activating autocrine pathways. In the present study, we investigated the mechanisms of invasive activity of EGF, HGF, and their synergistic effects in human ovarian cancer cells. Here our data suggest that EGF and HGF may use unique and overlapping signaling cascades leading to the invasive phenotype. We revealed that HGF-mediated cell migration and invasion required the coordinate activation of the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2. Although EGF-dependent invasive phenotype appeared to have similar requirements for phosphatidylinositol 3-kinase, this growth factor used the alternative p38 MAPK pathway for cell invasion. A significant role of p38 MAPK was further supported by the observation that expression of dominant negative p38 MAPK likewise inhibited EGF-dependent invasiveness and cell motility. We also showed that EGF cooperated with HGF to promote a highly invasive phenotype via the increased secretion of matrix metalloproteinase (MMP)-9. The coincident induction of MMP-9 was functionally significant because inclusion of MMP-9 inhibitor or an anti-MMP-9 neutralizing antibody abolished EGF- and HGF-induced cellular invasion. These findings provide insights into the mechanism of the malignant progression of ovarian cancer. Copyright © 2007 by The Endocrine Society.en_US
dc.languageengen_US
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_US
dc.relation.ispartofEndocrinologyen_US
dc.rightsEndocrinology. Copyright © The Endocrine Society.-
dc.subject.meshCarcinoma - Pathologyen_US
dc.subject.meshCell Movement - Drug Effectsen_US
dc.subject.meshCollagen - Metabolismen_US
dc.subject.meshDrug Combinationsen_US
dc.subject.meshDrug Evaluation, Preclinicalen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshEpidermal Growth Factor - Pharmacologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHepatocyte Growth Factor - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshLaminin - Metabolismen_US
dc.subject.meshMatrix Metalloproteinase 9 - Metabolismen_US
dc.subject.meshMitogen-Activated Protein Kinase 1 - Physiologyen_US
dc.subject.meshMitogen-Activated Protein Kinase 3 - Physiologyen_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshOvarian Neoplasms - Pathologyen_US
dc.subject.meshProteoglycans - Metabolismen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshP38 Mitogen-Activated Protein Kinases - Metabolism - Physiologyen_US
dc.titleSynergistic effects of epidermal growth factor and hepatocyte growth factor on human ovarian cancer cell invasion and migration: Role of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinaseen_US
dc.typeArticleen_US
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_US
dc.identifier.authorityWong, AST=rp00805en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1210/en.2007-0361en_US
dc.identifier.pmid17673518-
dc.identifier.scopuseid_2-s2.0-35548968519en_US
dc.identifier.hkuros130653-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-35548968519&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume148en_US
dc.identifier.issue11en_US
dc.identifier.spage5195en_US
dc.identifier.epage5208en_US
dc.identifier.isiWOS:000250444000010-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhou, HY=7404742310en_US
dc.identifier.scopusauthoridPon, YL=22235406500en_US
dc.identifier.scopusauthoridWong, AST=23987963300en_US

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