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Article: KIF7 attenuates prostate tumor growth through LKB1-mediated AKT inhibition

TitleKIF7 attenuates prostate tumor growth through LKB1-mediated AKT inhibition
Authors
KeywordsKIF7
tumor suppressor gene
prostate cancer
LKB1
Issue Date2017
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2017, v. 8 n. 33, p. 54558-54571 How to Cite?
AbstractThis study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel. Further analysis revealed that KIF7-CC enhanced LKB1 expression and phosphorylation at Ser428, which induced PTEN phosphorylation at Ser380/Thr382/383 and consequently blocked AKT phosphorylation at Ser473. Downregulation of LKB1 significantly attenuated the suppressive effects of KIF7-CC on cell proliferation, colony formation and AKT phosphorylation. Furthermore, our in vivo studies showed that KIF7-CC reduced prostate tumorigenesis in cell-derived xenografts. Downregulation of LKB1 abrogated the anti-tumor effects of KIF7-CC in these xenografts. Taken together, these findings provide the first evidence to support the role of KIF7 as a negative regulator that inhibits PCa development partially through LKB1-mediated AKT inhibition.
Persistent Identifierhttp://hdl.handle.net/10722/259640
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, KY-
dc.contributor.authorLiu, J-
dc.contributor.authorChan, KW-
dc.date.accessioned2018-09-03T04:11:18Z-
dc.date.available2018-09-03T04:11:18Z-
dc.date.issued2017-
dc.identifier.citationOncotarget, 2017, v. 8 n. 33, p. 54558-54571-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/259640-
dc.description.abstractThis study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel. Further analysis revealed that KIF7-CC enhanced LKB1 expression and phosphorylation at Ser428, which induced PTEN phosphorylation at Ser380/Thr382/383 and consequently blocked AKT phosphorylation at Ser473. Downregulation of LKB1 significantly attenuated the suppressive effects of KIF7-CC on cell proliferation, colony formation and AKT phosphorylation. Furthermore, our in vivo studies showed that KIF7-CC reduced prostate tumorigenesis in cell-derived xenografts. Downregulation of LKB1 abrogated the anti-tumor effects of KIF7-CC in these xenografts. Taken together, these findings provide the first evidence to support the role of KIF7 as a negative regulator that inhibits PCa development partially through LKB1-mediated AKT inhibition.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectKIF7-
dc.subjecttumor suppressor gene-
dc.subjectprostate cancer-
dc.subjectLKB1-
dc.titleKIF7 attenuates prostate tumor growth through LKB1-mediated AKT inhibition-
dc.typeArticle-
dc.identifier.emailWong, KY: kai@pathology.hku.hk-
dc.identifier.emailLiu, J: jingliue@hku.hk-
dc.identifier.emailChan, KW: kwchan@pathology.hku.hk-
dc.identifier.authorityChan, KW=rp00330-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.17421-
dc.identifier.pmid28903364-
dc.identifier.pmcidPMC5589603-
dc.identifier.hkuros289838-
dc.identifier.volume8-
dc.identifier.issue33-
dc.identifier.spage54558-
dc.identifier.epage54571-
dc.identifier.isiWOS:000407826100055-
dc.publisher.placeUnited States-

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