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Article: AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma
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TitleAXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma
 
AuthorsXu, MZ5 4
Chan, SW2
Liu, AM6 4
Wong, KF6 4
Fan, ST4
Chen, J5
Poon, RT4
Zender, L1
Lowe, SW3
Hong, W2
Luk, JM5 6 4
 
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
 
CitationOncogene, 2011, v. 30 n. 10, p. 1229-1240 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2010.504
 
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.
 
ISSN0950-9232
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
 
DOIhttp://dx.doi.org/10.1038/onc.2010.504
 
PubMed Central IDPMC3330262
 
ISI Accession Number IDWOS:000288202400009
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorXu, MZ
 
dc.contributor.authorChan, SW
 
dc.contributor.authorLiu, AM
 
dc.contributor.authorWong, KF
 
dc.contributor.authorFan, ST
 
dc.contributor.authorChen, J
 
dc.contributor.authorPoon, RT
 
dc.contributor.authorZender, L
 
dc.contributor.authorLowe, SW
 
dc.contributor.authorHong, W
 
dc.contributor.authorLuk, JM
 
dc.date.accessioned2011-07-27T01:36:54Z
 
dc.date.available2011-07-27T01:36:54Z
 
dc.date.issued2011
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationOncogene, 2011, v. 30 n. 10, p. 1229-1240 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2010.504
 
dc.identifier.citeulike8297310
 
dc.identifier.doihttp://dx.doi.org/10.1038/onc.2010.504
 
dc.identifier.epage1240
 
dc.identifier.hkuros187696
 
dc.identifier.isiWOS:000288202400009
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.

 
dc.identifier.issn0950-9232
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
 
dc.identifier.issue10
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3330262
 
dc.identifier.pmid21076472
 
dc.identifier.scopuseid_2-s2.0-79952532529
 
dc.identifier.spage1229
 
dc.identifier.urihttp://hdl.handle.net/10722/135547
 
dc.identifier.volume30
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofOncogene
 
dc.relation.referencesReferences in Scopus
 
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.subjectAXL receptor kinase
 
dc.subjectcancer signaling
 
dc.subjectHCC
 
dc.subjecthepatocellular carcinoma
 
dc.subjectHippo pathway
 
dc.subjectYAP1 oncogene
 
dc.titleAXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. Helmholtz Centre for Infection Research (HZI)
  2. Institute of Molecular and Cell Biology, A-Star, Singapore
  3. Howard Hughes Medical Institute
  4. The University of Hong Kong
  5. Nanjing Medical University
  6. National University of Singapore