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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

TitleIdentification of XAF1 as a novel cell cycle regulator through modulating G 2/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2009, v. 30 n. 9, p. 1507-1516 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/163273
ISSN
2014 Impact Factor: 5.334
2014 SCImago Journal Rankings: 2.152
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, Jen_HK
dc.contributor.authorGu, Qen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorZhang, Wen_HK
dc.contributor.authorYang, Men_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorChan, Sen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorJiang, Ben_HK
dc.contributor.authorTu, Sen_HK
dc.contributor.authorMa, Jen_HK
dc.contributor.authorHung, IFen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2012-09-05T05:29:30Z-
dc.date.available2012-09-05T05:29:30Z-
dc.date.issued2009en_HK
dc.identifier.citationCarcinogenesis, 2009, v. 30 n. 9, p. 1507-1516en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163273-
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.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.titleIdentification of XAF1 as a novel cell cycle regulator through modulating G 2/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal canceren_HK
dc.typeArticleen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailHung, IF: ivanhung@hkucc.hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityQiao, L=rp00513en_HK
dc.identifier.authorityHung, IF=rp00508en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/carcin/bgp155en_HK
dc.identifier.pmid19628579-
dc.identifier.scopuseid_2-s2.0-70249108452en_HK
dc.identifier.hkuros156656-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70249108452&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1507en_HK
dc.identifier.epage1516en_HK
dc.identifier.isiWOS:000269608200005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridGu, Q=24469982400en_HK
dc.identifier.scopusauthoridLi, M=36067425800en_HK
dc.identifier.scopusauthoridZhang, W=7409428339en_HK
dc.identifier.scopusauthoridYang, M=7404927250en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridChan, S=35071039700en_HK
dc.identifier.scopusauthoridQiao, L=7202151719en_HK
dc.identifier.scopusauthoridJiang, B=34770534200en_HK
dc.identifier.scopusauthoridTu, S=7202726555en_HK
dc.identifier.scopusauthoridMa, J=35275386200en_HK
dc.identifier.scopusauthoridHung, IF=7006103457en_HK
dc.identifier.scopusauthoridLan, HY=24544799000en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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