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Article: Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties

TitleTumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties
Authors
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2012, v. 31 n. 32, p. 3709-3720 How to Cite?
Abstract
Alpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor-suppressive critical region 11q22-23 and its downregulation is significantly associated with the progression of NPC. However, little is known about the functional impact of CRYAB on NPC progression. In this study we evaluated the NPC tumor-suppressive and progression-associated functions of CRYAB. Activation of CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB affected NPC progression-associated phenotypes such as loss of cell adhesion, invasion, interaction with the tumor microenvironment, invasive protrusion formation in three dimensional Matrigel culture, as well as expression of epithelial-mesenchymal transition-associated markers. CRYAB mediates this ability to suppress cancer progression by inhibition of E-cadherin cytoplasmic internalization and maintenance of beta-catenin in the membrane that subsequently reduces the levels of expression of critical downstream targets such as cyclin-D1 and c-myc. Both ectopically expressed and recombinant CRYAB proteins were associated with endogenous E-cadherin and beta-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB alpha-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and beta-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the beta-catenin function.
Persistent Identifierhttp://hdl.handle.net/10722/148670
ISSN
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
ISI Accession Number ID

 

Author Affiliations
  1. The University of Hong Kong
  2. Pamela Youde Nethersole Eastern Hospital
  3. UC Irvine
  4. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
  5. Södersjukhuset
DC FieldValueLanguage
dc.contributor.authorHuang, Zen_HK
dc.contributor.authorCheng, Yen_HK
dc.contributor.authorChiu, PMen_HK
dc.contributor.authorCheung, FMFen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorKwong, DLWen_HK
dc.contributor.authorLee, AWMen_HK
dc.contributor.authorZabarovsky, ERen_HK
dc.contributor.authorStanbridge, EJen_HK
dc.contributor.authorLung, HLen_HK
dc.contributor.authorLung, MLen_HK
dc.date.accessioned2012-05-29T06:14:33Z-
dc.date.available2012-05-29T06:14:33Z-
dc.date.issued2012en_HK
dc.identifier.citationOncogene, 2012, v. 31 n. 32, p. 3709-3720en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148670-
dc.description.abstractAlpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor-suppressive critical region 11q22-23 and its downregulation is significantly associated with the progression of NPC. However, little is known about the functional impact of CRYAB on NPC progression. In this study we evaluated the NPC tumor-suppressive and progression-associated functions of CRYAB. Activation of CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB affected NPC progression-associated phenotypes such as loss of cell adhesion, invasion, interaction with the tumor microenvironment, invasive protrusion formation in three dimensional Matrigel culture, as well as expression of epithelial-mesenchymal transition-associated markers. CRYAB mediates this ability to suppress cancer progression by inhibition of E-cadherin cytoplasmic internalization and maintenance of beta-catenin in the membrane that subsequently reduces the levels of expression of critical downstream targets such as cyclin-D1 and c-myc. Both ectopically expressed and recombinant CRYAB proteins were associated with endogenous E-cadherin and beta-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB alpha-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and beta-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the beta-catenin function.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.subject.meshAdherens Junctions - metabolism-
dc.subject.meshCadherins - metabolism-
dc.subject.meshCarcinoma - metabolism - pathology-
dc.subject.meshNasopharyngeal Neoplasms - metabolism - pathology-
dc.subject.meshTumor Suppressor Proteins - metabolism-
dc.titleTumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated propertiesen_HK
dc.typeArticleen_HK
dc.identifier.emailCheng, Y: yuecheng@hku.hken_HK
dc.identifier.emailChiu, PM: h9994065@hkusua.hku.hken_HK
dc.identifier.emailNicholls, JM: nicholls@pathology.hku.hken_HK
dc.identifier.emailKwong, DLW: dlwkwong@hkucc.hku.hken_HK
dc.identifier.emailLung, HL: hllung2@hku.hken_HK
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityCheng, Y=rp01320en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityKwong, DLW=rp00414en_HK
dc.identifier.authorityLung, HL=rp00299en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2011.529en_HK
dc.identifier.pmid22158051-
dc.identifier.scopuseid_2-s2.0-84864946374en_HK
dc.identifier.hkuros199894-
dc.identifier.hkuros210082-
dc.identifier.volume31-
dc.identifier.issue32-
dc.identifier.spage3709-
dc.identifier.epage3720-
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000307653800005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK
dc.identifier.scopusauthoridLung, HL=6603819904en_HK
dc.identifier.scopusauthoridStanbridge, EJ=35726268300en_HK
dc.identifier.scopusauthoridZabarovsky, ER=35331513900en_HK
dc.identifier.scopusauthoridLee, AWM=38461355700en_HK
dc.identifier.scopusauthoridKwong, DLW=15744231600en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridCheung, FMF=7102329474en_HK
dc.identifier.scopusauthoridChiu, PM=54583235000en_HK
dc.identifier.scopusauthoridCheng, Y=36131038300en_HK
dc.identifier.scopusauthoridHuang, Z=8514510100en_HK

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