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Conference Paper: XAF1 induced mitotic catastrophe through modulation of G2/M checkpoint and interaction with checkpoint kinase 1

TitleXAF1 induced mitotic catastrophe through modulation of G2/M checkpoint and interaction with checkpoint kinase 1
Authors
Issue Date2009
PublisherW.B. Saunders Co.
Citation
Digestive Disease Week 2009, Chicago, IL, 31 May - 5 June 2009. In Gastroenterology, 2009, v. 136 n. 5 S1, p. A754 Abstract no. W1922 How to Cite?
AbstractBackground: XAF1 was first recognized as an antagonist in XIAP-suppressed caspase 3 activity. It has lower expression in cancer cells than normal tissue and sensitizes TRAILand etoposide-triggered apoptosis. However, its role in cell growth and the underlying mechanism have not been studied. Methods: Transfectants of gastrointestinal cancer cell lines AGS, Lovo and SW1116 stably expressing XAF1 and vector control were established. Cell growth, apoptosis, morphology, mitotic status and cell cycle distribution were assessed. Mitotic catastrophe was identified by occurrence of aberrant nuclei and centrosomal amplification. The expression and activity of G2/M proteins were detected by immunoblotting and kinase assay. Interaction between XAF1 and checkpoint kinase 1 (Chk1), was demonstrated by co-immunoprecipitation and the subcellular co-localization while the role of Chk1 in XAF1-induced G2/M arrest was evaluated by RNA interference. Results: Over-expression of XAF1 suppressed serum-dependent cancer cell growth, induced cell accumulation in mitosis, mitotic catastrophe and G2/M cell cycle arrest. Interestingly, XAF1 was only expressed in G2/M phase after cell cycle synchronization. In addition, XAF1 interacted with and activated Chk1, inactivated Cdc25C, and Cdc2/cyclin B complex. Suppression of Chk1 abrogated XAF1-induced G2/M arrest. Furthermore, over-expression of XAF1 increased the susceptibility of cancer cell to serum-deprivation-induced apoptosis. Conclusions: These findings suggest that XAF1 promotes apoptosis secondary to mitotic catastrophe through modulating G2/M checkpoint, implicating a novel XIAP-independent function pathway of XAF1. Low expression of XAF1 in cancer cell might correlate to the surveillance defect of transformed cell in gastrointestinal tract, thus inferring XAF1 as a potential target for the therapy of gastrointestinal cancers.
Persistent Identifierhttp://hdl.handle.net/10722/62378
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170

 

DC FieldValueLanguage
dc.contributor.authorWang, Jen_HK
dc.contributor.authorZhang, Wen_HK
dc.contributor.authorGu, Qen_HK
dc.contributor.authorLi, Zen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-07-13T03:59:58Z-
dc.date.available2010-07-13T03:59:58Z-
dc.date.issued2009en_HK
dc.identifier.citationDigestive Disease Week 2009, Chicago, IL, 31 May - 5 June 2009. In Gastroenterology, 2009, v. 136 n. 5 S1, p. A754 Abstract no. W1922en_HK
dc.identifier.issn0016-5085-
dc.identifier.urihttp://hdl.handle.net/10722/62378-
dc.description.abstractBackground: XAF1 was first recognized as an antagonist in XIAP-suppressed caspase 3 activity. It has lower expression in cancer cells than normal tissue and sensitizes TRAILand etoposide-triggered apoptosis. However, its role in cell growth and the underlying mechanism have not been studied. Methods: Transfectants of gastrointestinal cancer cell lines AGS, Lovo and SW1116 stably expressing XAF1 and vector control were established. Cell growth, apoptosis, morphology, mitotic status and cell cycle distribution were assessed. Mitotic catastrophe was identified by occurrence of aberrant nuclei and centrosomal amplification. The expression and activity of G2/M proteins were detected by immunoblotting and kinase assay. Interaction between XAF1 and checkpoint kinase 1 (Chk1), was demonstrated by co-immunoprecipitation and the subcellular co-localization while the role of Chk1 in XAF1-induced G2/M arrest was evaluated by RNA interference. Results: Over-expression of XAF1 suppressed serum-dependent cancer cell growth, induced cell accumulation in mitosis, mitotic catastrophe and G2/M cell cycle arrest. Interestingly, XAF1 was only expressed in G2/M phase after cell cycle synchronization. In addition, XAF1 interacted with and activated Chk1, inactivated Cdc25C, and Cdc2/cyclin B complex. Suppression of Chk1 abrogated XAF1-induced G2/M arrest. Furthermore, over-expression of XAF1 increased the susceptibility of cancer cell to serum-deprivation-induced apoptosis. Conclusions: These findings suggest that XAF1 promotes apoptosis secondary to mitotic catastrophe through modulating G2/M checkpoint, implicating a novel XIAP-independent function pathway of XAF1. Low expression of XAF1 in cancer cell might correlate to the surveillance defect of transformed cell in gastrointestinal tract, thus inferring XAF1 as a potential target for the therapy of gastrointestinal cancers.-
dc.languageengen_HK
dc.publisherW.B. Saunders Co.-
dc.relation.ispartofGastroenterology-
dc.titleXAF1 induced mitotic catastrophe through modulation of G2/M checkpoint and interaction with checkpoint kinase 1en_HK
dc.typeConference_Paperen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailZhang, W: wenjingzhang307@163.comen_HK
dc.identifier.emailGu, Q: qingappl@hotmail.comen_HK
dc.identifier.emailLi, Z: lzssc@yahoo.comen_HK
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailLan, HY: hylan@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.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S0016-5085(09)63481-8-
dc.identifier.hkuros155726en_HK

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