File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer

TitleReduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer
Authors
Issue Date2014
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
Citation
Molecular Cancer, 2014, v. 13, p. article no. 49 How to Cite?
AbstractAMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-beta1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-beta1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-beta1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-beta1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-beta1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-beta1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-beta1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-beta1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer.
Persistent Identifierhttp://hdl.handle.net/10722/195911
ISSN
2015 Impact Factor: 5.888
2015 SCImago Journal Rankings: 2.337
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Cen_US
dc.contributor.authorLiu, VWSen_US
dc.contributor.authorChiu, PMen_US
dc.contributor.authorYao, KMen_US
dc.contributor.authorNgan, HYSen_US
dc.contributor.authorChan, DWen_US
dc.date.accessioned2014-03-21T02:18:56Z-
dc.date.available2014-03-21T02:18:56Z-
dc.date.issued2014en_US
dc.identifier.citationMolecular Cancer, 2014, v. 13, p. article no. 49en_US
dc.identifier.issn1476-4598-
dc.identifier.urihttp://hdl.handle.net/10722/195911-
dc.description.abstractAMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-beta1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-beta1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-beta1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-beta1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-beta1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-beta1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-beta1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-beta1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer.en_US
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.comen_US
dc.relation.ispartofMolecular Canceren_US
dc.rightsMolecular Cancer. Copyright © BioMed Central Ltd.en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleReduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian canceren_US
dc.typeArticleen_US
dc.identifier.emailLiu, VWS: vwsliu@hku.hken_US
dc.identifier.emailChiu, PM: h9994065@hkusua.hku.hken_US
dc.identifier.emailYao, KM: kmyao@hku.hken_US
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_US
dc.identifier.emailChan, DW: dwchan@hku.hken_US
dc.identifier.authorityLiu, VWS=rp00341en_US
dc.identifier.authorityYao, KM=rp00344en_US
dc.identifier.authorityNgan, HYS=rp00346en_US
dc.identifier.authorityChan, DW=rp00543en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1476-4598-13-49-
dc.identifier.pmid24602453-
dc.identifier.hkuros228305en_US
dc.identifier.volume13en_US
dc.identifier.spagearticle no. 49en_US
dc.identifier.epagearticle no. 49en_US
dc.identifier.isiWOS:000334540700003-
dc.publisher.placeUnited Kingdomen_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats