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Article: Suppression of androgen-independent prostate cancer cell aggressiveness by FTY720: Validating Runx2 as a potential antimetastatic drug screening platform

TitleSuppression of androgen-independent prostate cancer cell aggressiveness by FTY720: Validating Runx2 as a potential antimetastatic drug screening platform
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2009, v. 15 n. 13, p. 4322-4335 How to Cite?
AbstractPurpose: Previously, FTY720 was found to possess potent anticancer effects on various types of cancer. In the present study, we aimed to first verify the role of Runx2 in prostate cancer progression and metastasis, and, subsequently, assessed if FTY720 could modulate Runx2 expression, thus interfering downstream events regulated by this protein. Experimental Design: First, the association between Runx2 and prostate cancer progression was assessed using localized prostate cancer specimens and mechanistic investigation of Runx2-induced cancer aggressiveness was then carried out. Subsequently, the effect of FTY720 on Runx2 expression and transcriptionala ctivity was investigated using PC-3 cells, which highly expressed Runx2 protein. Last, the involvement of Runx2 in FTY720-induced anticancer effects was evaluated by modulating Runx2 expression in various prostate cancer cell lines. Results: Runx2 nuclear expression was found to be up-regulated in prostate cancer and its expression could be used as a predictor of metastasis in prostate cancer. Furthermechanistic studies indicated that Runx2 accelerated prostate cancer aggressiveness through promotion of cadherin switching, invasion toward collagen I, and Akt activation. Subsequently, we found that FTY720 treatment down-regulated Runx2 expression and its transcriptional activity, as well as inhibited its regulated downstream events.More importantly, silencing Runx2 in PC-3 enhanced FTY720-induced anticancer effects as well as cell viability inhibition, whereas overexpressing Runx2 in 22Rv1that expressed very low endogenous Runx2 protein conferred resistance in the same events. Conclusion: This study provided a novelmec hanism for the anticancer effect of FTY720 on advanced prostate cancer, thus highlighting the therapeutic potential of this drug in treating this disease. © 2009 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/67712
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID
Funding AgencyGrant Number
RGCHKU7490/03M
HKU7470/04M
HKU Foundation Seed Funding
NSFC/RGC
NHKU738/03
Funding Information:

RGC grants HKU7490/03M, HKU7470/04M, HKU Foundation Seed Funding/03, NSFC/RGC, NHKU738/03 (YC.Wong).

References

 

DC FieldValueLanguage
dc.contributor.authorChua, CWen_HK
dc.contributor.authorChiu, YTen_HK
dc.contributor.authorYuen, HFen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-06T05:57:35Z-
dc.date.available2010-09-06T05:57:35Z-
dc.date.issued2009en_HK
dc.identifier.citationClinical Cancer Research, 2009, v. 15 n. 13, p. 4322-4335en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67712-
dc.description.abstractPurpose: Previously, FTY720 was found to possess potent anticancer effects on various types of cancer. In the present study, we aimed to first verify the role of Runx2 in prostate cancer progression and metastasis, and, subsequently, assessed if FTY720 could modulate Runx2 expression, thus interfering downstream events regulated by this protein. Experimental Design: First, the association between Runx2 and prostate cancer progression was assessed using localized prostate cancer specimens and mechanistic investigation of Runx2-induced cancer aggressiveness was then carried out. Subsequently, the effect of FTY720 on Runx2 expression and transcriptionala ctivity was investigated using PC-3 cells, which highly expressed Runx2 protein. Last, the involvement of Runx2 in FTY720-induced anticancer effects was evaluated by modulating Runx2 expression in various prostate cancer cell lines. Results: Runx2 nuclear expression was found to be up-regulated in prostate cancer and its expression could be used as a predictor of metastasis in prostate cancer. Furthermechanistic studies indicated that Runx2 accelerated prostate cancer aggressiveness through promotion of cadherin switching, invasion toward collagen I, and Akt activation. Subsequently, we found that FTY720 treatment down-regulated Runx2 expression and its transcriptional activity, as well as inhibited its regulated downstream events.More importantly, silencing Runx2 in PC-3 enhanced FTY720-induced anticancer effects as well as cell viability inhibition, whereas overexpressing Runx2 in 22Rv1that expressed very low endogenous Runx2 protein conferred resistance in the same events. Conclusion: This study provided a novelmec hanism for the anticancer effect of FTY720 on advanced prostate cancer, thus highlighting the therapeutic potential of this drug in treating this disease. © 2009 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.en_HK
dc.relation.ispartofClinical Cancer Researchen_HK
dc.subject.meshCore Binding Factor Alpha 1 Subunit - metabolism - physiology-
dc.subject.meshDrug Screening Assays, Antitumor - methods-
dc.subject.meshPropylene Glycols - pharmacology - therapeutic use-
dc.subject.meshProstatic Intraepithelial Neoplasia - genetics - metabolism - pathology-
dc.subject.meshProstatic Neoplasms - drug therapy - genetics - metabolism - pathology-
dc.titleSuppression of androgen-independent prostate cancer cell aggressiveness by FTY720: Validating Runx2 as a potential antimetastatic drug screening platformen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-0432&volume=15&issue=13&spage=4322&epage=4335&date=2009&atitle=Suppression+of+androgen-independent+prostate+cancer+cell+aggressiveness+by+FTY720:+validating+Runx2+as+a+potential+antimetastatic+drug+screening+platformen_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailMan, K: kwanman@hkucc.hku.hken_HK
dc.identifier.emailLing, MT: patling@hkucc.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-08-3157en_HK
dc.identifier.pmid19509141-
dc.identifier.scopuseid_2-s2.0-67650369580en_HK
dc.identifier.hkuros163933en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650369580&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue13en_HK
dc.identifier.spage4322en_HK
dc.identifier.epage4335en_HK
dc.identifier.isiWOS:000268908300012-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChua, CW=9437494600en_HK
dc.identifier.scopusauthoridChiu, YT=23975797700en_HK
dc.identifier.scopusauthoridYuen, HF=14018633400en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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