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Article: Identification of XAF1 as a novel cell cycle regulator through modulating G 2/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer
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TitleIdentification of XAF1 as a novel cell cycle regulator through modulating G 2/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer
 
AuthorsWang, J1 2
Gu, Q2
Li, M2
Zhang, W1 2
Yang, M2
Zou, B2
Chan, S2
Qiao, L2
Jiang, B2
Tu, S2
Ma, J2
Hung, IF2
Lan, HY2
Wong, BCY2
 
Issue Date2009
 
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
CitationCarcinogenesis, 2009, v. 30 n. 9, p. 1507-1516 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgp155
 
AbstractBackground and aims: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) was first recognized as an antagonist of X-linked inhibitor of apoptosis in suppressing caspase 3 activity. It has lower expression in cancer cells than normal tissue. Overexpression of XAF1 can inhibit cancer cell growth and sensitize tumor necrosis factor-related apoptosis-inducing ligand- or etoposide-induced apoptosis. The aim of this study is to elucidate the mechanism of XAF1 in regulating cell growth. Methods: Stable transfectants of gastrointestinal (GI) cancer cell lines AGS and SW1116 expressing XAF1 and vector control were generated. Cell growth, apoptosis, mitotic status and cell cycle distribution were assessed. The interaction between XAF1 and G 2/M checkpoint proteins was evaluated by immunoblotting, kinase assay and co-immunoprecipitation assay. Mitotic catastrophe was identified by occurrence of aberrant nuclei and centrosomal amplification. Results: Our results showed that overexpression of XAF1 suppressed serum-dependent cancer cell growth, induced mitotic catastrophe and G 2/M cell cycle arrest. Interestingly, XAF1 was predominantly expressed in G 2/M phase after cell cycle synchronization. XAF1 interacted with and activated checkpoint kinase 1 (Chk1), inactivated Cdc25C and lead to inactivation of Cdc2-cyclin B complex. Suppression of Chk1 abrogated XAF1-induced G 2/M arrest. Conclusions: Our findings implicate XAF1 as a novel cell cycle modulator that is recruited in G 2/M phase and thus unravel a novel function pathway of XAF1, suggesting the potential role of XAF1 as the target for the management of GI cancers. © The Author 2009. Published by Oxford University Press. All rights reserved.
 
ISSN0143-3334
2012 Impact Factor: 5.635
2012 SCImago Journal Rankings: 2.349
 
DOIhttp://dx.doi.org/10.1093/carcin/bgp155
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWang, J
 
dc.contributor.authorGu, Q
 
dc.contributor.authorLi, M
 
dc.contributor.authorZhang, W
 
dc.contributor.authorYang, M
 
dc.contributor.authorZou, B
 
dc.contributor.authorChan, S
 
dc.contributor.authorQiao, L
 
dc.contributor.authorJiang, B
 
dc.contributor.authorTu, S
 
dc.contributor.authorMa, J
 
dc.contributor.authorHung, IF
 
dc.contributor.authorLan, HY
 
dc.contributor.authorWong, BCY
 
dc.date.accessioned2012-09-05T05:29:30Z
 
dc.date.available2012-09-05T05:29:30Z
 
dc.date.issued2009
 
dc.description.abstractBackground and aims: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) was first recognized as an antagonist of X-linked inhibitor of apoptosis in suppressing caspase 3 activity. It has lower expression in cancer cells than normal tissue. Overexpression of XAF1 can inhibit cancer cell growth and sensitize tumor necrosis factor-related apoptosis-inducing ligand- or etoposide-induced apoptosis. The aim of this study is to elucidate the mechanism of XAF1 in regulating cell growth. Methods: Stable transfectants of gastrointestinal (GI) cancer cell lines AGS and SW1116 expressing XAF1 and vector control were generated. Cell growth, apoptosis, mitotic status and cell cycle distribution were assessed. The interaction between XAF1 and G 2/M checkpoint proteins was evaluated by immunoblotting, kinase assay and co-immunoprecipitation assay. Mitotic catastrophe was identified by occurrence of aberrant nuclei and centrosomal amplification. Results: Our results showed that overexpression of XAF1 suppressed serum-dependent cancer cell growth, induced mitotic catastrophe and G 2/M cell cycle arrest. Interestingly, XAF1 was predominantly expressed in G 2/M phase after cell cycle synchronization. XAF1 interacted with and activated checkpoint kinase 1 (Chk1), inactivated Cdc25C and lead to inactivation of Cdc2-cyclin B complex. Suppression of Chk1 abrogated XAF1-induced G 2/M arrest. Conclusions: Our findings implicate XAF1 as a novel cell cycle modulator that is recruited in G 2/M phase and thus unravel a novel function pathway of XAF1, suggesting the potential role of XAF1 as the target for the management of GI cancers. © The Author 2009. Published by Oxford University Press. All rights reserved.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationCarcinogenesis, 2009, v. 30 n. 9, p. 1507-1516 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgp155
 
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgp155
 
dc.identifier.epage1516
 
dc.identifier.hkuros156656
 
dc.identifier.issn0143-3334
2012 Impact Factor: 5.635
2012 SCImago Journal Rankings: 2.349
 
dc.identifier.issue9
 
dc.identifier.pmid19628579
 
dc.identifier.scopuseid_2-s2.0-70249108452
 
dc.identifier.spage1507
 
dc.identifier.urihttp://hdl.handle.net/10722/163273
 
dc.identifier.volume30
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofCarcinogenesis
 
dc.relation.referencesReferences in Scopus
 
dc.titleIdentification of XAF1 as a novel cell cycle regulator through modulating G 2/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer
 
dc.typeArticle
 
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<contributor.author>Yang, M</contributor.author>
<contributor.author>Zou, B</contributor.author>
<contributor.author>Chan, S</contributor.author>
<contributor.author>Qiao, L</contributor.author>
<contributor.author>Jiang, B</contributor.author>
<contributor.author>Tu, S</contributor.author>
<contributor.author>Ma, J</contributor.author>
<contributor.author>Hung, IF</contributor.author>
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<description.abstract>Background and aims: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) was first recognized as an antagonist of X-linked inhibitor of apoptosis in suppressing caspase 3 activity. It has lower expression in cancer cells than normal tissue. Overexpression of XAF1 can inhibit cancer cell growth and sensitize tumor necrosis factor-related apoptosis-inducing ligand- or etoposide-induced apoptosis. The aim of this study is to elucidate the mechanism of XAF1 in regulating cell growth. Methods: Stable transfectants of gastrointestinal (GI) cancer cell lines AGS and SW1116 expressing XAF1 and vector control were generated. Cell growth, apoptosis, mitotic status and cell cycle distribution were assessed. The interaction between XAF1 and G 2/M checkpoint proteins was evaluated by immunoblotting, kinase assay and co-immunoprecipitation assay. Mitotic catastrophe was identified by occurrence of aberrant nuclei and centrosomal amplification. Results: Our results showed that overexpression of XAF1 suppressed serum-dependent cancer cell growth, induced mitotic catastrophe and G 2/M cell cycle arrest. Interestingly, XAF1 was predominantly expressed in G 2/M phase after cell cycle synchronization. XAF1 interacted with and activated checkpoint kinase 1 (Chk1), inactivated Cdc25C and lead to inactivation of Cdc2-cyclin B complex. Suppression of Chk1 abrogated XAF1-induced G 2/M arrest. Conclusions: Our findings implicate XAF1 as a novel cell cycle modulator that is recruited in G 2/M phase and thus unravel a novel function pathway of XAF1, suggesting the potential role of XAF1 as the target for the management of GI cancers. &#169; The Author 2009. Published by Oxford University Press. All rights reserved.</description.abstract>
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Author Affiliations
  1. Southern Medical University
  2. The University of Hong Kong