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dc.contributor.authorShin, E.
dc.contributor.authorHay, H.
dc.contributor.authorLee, M.
dc.contributor.authorGoh, J.
dc.contributor.authorTan, T.
dc.contributor.authorSen, Y.
dc.contributor.authorLim, S.
dc.contributor.authorYousef, E.
dc.contributor.authorOng, H.
dc.contributor.authorThike, A.
dc.contributor.authorKong, X.
dc.contributor.authorWu, Z.
dc.contributor.authorMendoz, E.
dc.contributor.authorSun, W.
dc.contributor.authorSalto-Tellez, M.
dc.contributor.authorLim, C.
dc.contributor.authorLobie, P.
dc.contributor.authorLim, Y.
dc.contributor.authorYap, C.
dc.contributor.authorZeng, Q.
dc.contributor.authorSethi, G.
dc.contributor.authorLee, M.
dc.contributor.authorTan, P.
dc.contributor.authorGoh, B.
dc.contributor.authorMiller, L.
dc.contributor.authorThiery, J.
dc.contributor.authorZhu, T.
dc.contributor.authorGaboury, L.
dc.contributor.authorTan, P.
dc.contributor.authorHui, K.
dc.contributor.authorYip, G.
dc.contributor.authorMiyamoto, S.
dc.contributor.authorKumar, Alan Prem
dc.contributor.authorTergaonkar, V.
dc.date.accessioned2017-03-17T08:29:30Z
dc.date.available2017-03-17T08:29:30Z
dc.date.created2017-02-19T19:31:48Z
dc.date.issued2014
dc.identifier.citationShin, E. and Hay, H. and Lee, M. and Goh, J. and Tan, T. and Sen, Y. and Lim, S. et al. 2014. DEAD-box helicase DP103 defines metastatic potential of human breast cancers. Journal of Clinical Investigation. 124 (9): pp. 3807-3824.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/51066
dc.identifier.doi10.1172/JCI73451
dc.description.abstract

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β–activated kinase-1 (TAK1) phosphorylation of NF-κB–activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB–mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

dc.publisherAmerican Society for Clinical Investigation
dc.titleDEAD-box helicase DP103 defines metastatic potential of human breast cancers
dc.typeJournal Article
dcterms.source.volume124
dcterms.source.number9
dcterms.source.startPage3807
dcterms.source.endPage3824
dcterms.source.issn0021-9738
dcterms.source.titleJournal of Clinical Investigation
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access via publisher


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