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Article: AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma

TitleAXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma
Authors
KeywordsAXL receptor kinase
cancer signaling
HCC
hepatocellular carcinoma
Hippo pathway
YAP1 oncogene
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2011, v. 30 n. 10, p. 1229-1240 How to Cite?
Abstract
Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC. © 2011 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/135547
ISSN
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Biomedical Research Grants Council of Singapore
National University Cancer Institute (NCIS) Centre
National Natural Science Foundation of China81000880
National Cancer Institute of NIHCA13106
A*STAR
Funding Information:

Sources of support: The work was supported by grants to JML from the Biomedical Research Grants Council of Singapore and by the National University Cancer Institute (NCIS) Centre Grant; WH was supported by the A*STAR and MX by the National Natural Science Foundation of China (Grant No. 81000880). SWL is an investigator in the Howard Hughes Medical Institute and Dr Lowe's work is supported by a program grant (CA13106) from the National Cancer Institute of NIH.

References

 

DC FieldValueLanguage
dc.contributor.authorXu, MZen_HK
dc.contributor.authorChan, SWen_HK
dc.contributor.authorLiu, AMen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorChen, Jen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorZender, Len_HK
dc.contributor.authorLowe, SWen_HK
dc.contributor.authorHong, Wen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2011-07-27T01:36:54Z-
dc.date.available2011-07-27T01:36:54Z-
dc.date.issued2011en_HK
dc.identifier.citationOncogene, 2011, v. 30 n. 10, p. 1229-1240en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135547-
dc.description.abstractYes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC. © 2011 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectAXL receptor kinaseen_HK
dc.subjectcancer signalingen_HK
dc.subjectHCCen_HK
dc.subjecthepatocellular carcinomaen_HK
dc.subjectHippo pathwayen_HK
dc.subjectYAP1 oncogeneen_HK
dc.subject.meshCarcinoma, Hepatocellular - genetics - metabolism-
dc.subject.meshCell Transformation, Neoplastic - genetics - metabolism-
dc.subject.meshLiver Neoplasms - genetics - metabolism-
dc.subject.meshNuclear Proteins - genetics - metabolism-
dc.subject.meshProto-Oncogene Proteins - genetics - metabolism-
dc.titleAXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=30&issue=10&spage=1229&epage=1240&date=2011&atitle=AXL+receptor+kinase+is+a+mediator+of+YAP-dependent+oncogenic+functions+in+hepatocellular+carcinoma-
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailPoon, RT: poontp@hkucc.hku.hken_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/onc.2010.504en_HK
dc.identifier.pmid21076472en_HK
dc.identifier.pmcidPMC3330262-
dc.identifier.scopuseid_2-s2.0-79952532529en_HK
dc.identifier.hkuros187696en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952532529&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1229en_HK
dc.identifier.epage1240en_HK
dc.identifier.isiWOS:000288202400009-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridXu, MZ=24339881700en_HK
dc.identifier.scopusauthoridChan, SW=36901162300en_HK
dc.identifier.scopusauthoridLiu, AM=36134439500en_HK
dc.identifier.scopusauthoridWong, KF=35081410800en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridChen, J=38662182300en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK
dc.identifier.scopusauthoridZender, L=6603035987en_HK
dc.identifier.scopusauthoridLowe, SW=15064198100en_HK
dc.identifier.scopusauthoridHong, W=7401528059en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.citeulike8297310-

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