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Article: Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas

TitleAberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas
Authors
Issue Date2014
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/lungcan
Citation
Lung Cancer, 2014, v. 85 n. 2, p. 282-292 How to Cite?
AbstractBACKGROUND: Large tumor suppressor 2 (LATS2) gene is a putative tumor suppressor gene with potential roles in regulation of cell proliferation and apoptosis in lung cancer. The aim of this study is to explore the association of aberrant LATS2 expression with EGFR mutation and survival in lung adenocarcinoma (AD), and the effects of LATS2 silencing in both lung AD cell lines. METHODS: LATS2 mRNA and protein expression in resected lung AD were correlated with demographic characteristics, EGFR mutation and survival. LATS2-specific siRNA was transfected into four EGFR wild-type (WT) and three EGFR mutant AD cell lines and the changes in LATS2 expression and relevant signaling molecules before and after LATS2 knockdown were assayed. RESULTS: Fifty resected lung AD were included (M:F=23:27, smokers:non-smokers=19:31, EGFR mutant:wild-type=21:29) with LATS2 mRNA levels showed no significant difference between gender, age, smoking and pathological stages while LATS2 immunohistochemical staining on an independent set of 79 lung AD showed similar trend. LATS2 mRNA level was found to be a significant independent predictor for survival status (disease-free survival RR=0.217; p=0.003; Overall survival RR=0.238; p=0.036). siRNA-mediated suppression of LATS2 expression resulted in augmentation of ERK phosphorylation in EGFR wild-type AD cell lines with high basal LATS2 expression, discriminatory modulation of Akt signaling between EGFR wild-type and mutant cells, and induction of p53 accumulation in AD cell lines with low baseline p53 levels. CONCLUSIONS: LATS2 expression level is predictive of survival in patients with resected lung AD. LATS2 may modulate and contribute to tumor growth via different signaling pathways in EGFR mutant and wild-type tumors.
Persistent Identifierhttp://hdl.handle.net/10722/202501
ISSN
2015 Impact Factor: 3.767
2015 SCImago Journal Rankings: 1.923
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLUO, SY-
dc.contributor.authorSit, AKY-
dc.contributor.authorSihoe, DLA-
dc.contributor.authorSuen, WS-
dc.contributor.authorAu, TWK-
dc.contributor.authorTang, X-
dc.contributor.authorMa, ESK-
dc.contributor.authorChan, WK-
dc.contributor.authorWistuba, II-
dc.contributor.authorMinna, JD-
dc.contributor.authorTsao, GSW-
dc.contributor.authorLam, CLD-
dc.date.accessioned2014-09-19T08:08:26Z-
dc.date.available2014-09-19T08:08:26Z-
dc.date.issued2014-
dc.identifier.citationLung Cancer, 2014, v. 85 n. 2, p. 282-292-
dc.identifier.issn0169-5002-
dc.identifier.urihttp://hdl.handle.net/10722/202501-
dc.description.abstractBACKGROUND: Large tumor suppressor 2 (LATS2) gene is a putative tumor suppressor gene with potential roles in regulation of cell proliferation and apoptosis in lung cancer. The aim of this study is to explore the association of aberrant LATS2 expression with EGFR mutation and survival in lung adenocarcinoma (AD), and the effects of LATS2 silencing in both lung AD cell lines. METHODS: LATS2 mRNA and protein expression in resected lung AD were correlated with demographic characteristics, EGFR mutation and survival. LATS2-specific siRNA was transfected into four EGFR wild-type (WT) and three EGFR mutant AD cell lines and the changes in LATS2 expression and relevant signaling molecules before and after LATS2 knockdown were assayed. RESULTS: Fifty resected lung AD were included (M:F=23:27, smokers:non-smokers=19:31, EGFR mutant:wild-type=21:29) with LATS2 mRNA levels showed no significant difference between gender, age, smoking and pathological stages while LATS2 immunohistochemical staining on an independent set of 79 lung AD showed similar trend. LATS2 mRNA level was found to be a significant independent predictor for survival status (disease-free survival RR=0.217; p=0.003; Overall survival RR=0.238; p=0.036). siRNA-mediated suppression of LATS2 expression resulted in augmentation of ERK phosphorylation in EGFR wild-type AD cell lines with high basal LATS2 expression, discriminatory modulation of Akt signaling between EGFR wild-type and mutant cells, and induction of p53 accumulation in AD cell lines with low baseline p53 levels. CONCLUSIONS: LATS2 expression level is predictive of survival in patients with resected lung AD. LATS2 may modulate and contribute to tumor growth via different signaling pathways in EGFR mutant and wild-type tumors.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/lungcan-
dc.relation.ispartofLung Cancer-
dc.rights© <year>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas-
dc.typeArticle-
dc.identifier.emailSihoe, DLA: adls1@hku.hk-
dc.identifier.emailAu, TWK: auwkt@hkucc.hku.hk-
dc.identifier.emailMa, ESK: eskma@hkucc.hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailLam, CLD: dcllam@hku.hk-
dc.identifier.authoritySihoe, DLA=rp01889-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityLam, CLD=rp01345-
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.lungcan.2014.05.025-
dc.identifier.pmid24976335-
dc.identifier.scopuseid_2-s2.0-84904112321-
dc.identifier.hkuros237758-
dc.identifier.volume85-
dc.identifier.issue2-
dc.identifier.spage282-
dc.identifier.epage292-
dc.identifier.isiWOS:000340014700029-
dc.publisher.placeIreland-

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