HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer

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dc.contributor.authorClements, Miranda E.en
dc.contributor.authorHoltslander, Laurenen
dc.contributor.authorEdwards, Courtneyen
dc.contributor.authorTodd, Veraen
dc.contributor.authorDooyema, Samuel D. R.en
dc.contributor.authorBullock, Kennadyen
dc.contributor.authorBergdorf, Kenseyen
dc.contributor.authorZahnow, Cynthia A.en
dc.contributor.authorConnolly, Roisin M.en
dc.contributor.authorJohnson, Rachelle W.en
dc.contributor.funderU.S. Department of Defenseen
dc.contributor.funderNational Institutes of Healthen
dc.date.accessioned2023-04-18T15:34:20Z
dc.date.available2023-04-18T15:34:20Z
dc.date.issued2021-07-10en
dc.description.abstractDespite advances in breast cancer treatment, residual disease driven by dormant tumor cells continues to be a significant clinical problem. Leukemia inhibitory factor receptor (LIFR) promotes a dormancy phenotype in breast cancer cells and LIFR loss is correlated with poor patient survival. Herein, we demonstrate that histone deacetylase inhibitors (HDACi), which are in phase III clinical trials for breast cancer, epigenetically induced LIFR and activated a pro-dormancy program in breast cancer cells. HDACi slowed breast cancer cell proliferation and reduced primary tumor growth. Primary breast tumors from HDACi-treated patients had increased LIFR levels and reduced proliferation rates compared to pre-treatment levels. Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.en
dc.description.sponsorshipU.S. Department of Defense (Breakthrough Award W81XWH-18-1-0029); National Institutes of Health (R00CA194198; P30CA068485)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationClements, M. E., Holtslander, L., Edwards, C., Todd, V., Dooyema, S. D., Bullock, K., Bergdorf, K., Zahnow, C. A., Connolly, R. M. and Johnson, R. W. (2021) ‘HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer’, Oncogene, 40(34), pp.5314-5326. doi: 10.1038/s41388-021-01931-1en
dc.identifier.doi10.1038/s41388-021-01931-1en
dc.identifier.eissn1476-5594en
dc.identifier.endpage5326en
dc.identifier.issn0950-9232en
dc.identifier.issued34en
dc.identifier.journaltitleOncogeneen
dc.identifier.startpage5314en
dc.identifier.urihttps://hdl.handle.net/10468/14389
dc.identifier.volume40en
dc.language.isoenen
dc.publisherSpringer Nature Switzerland AGen
dc.rights© 2021, the Authors, under exclusive licence to Springer Nature B.V. This is a post-peer-review, pre-copyedit version of an article published in Oncogene. The final authenticated version is available online at: https://doi.org/10.1038/s41388-021-01931-1en
dc.subjectHDACien
dc.subjectDormancyen
dc.subjectBreast canceren
dc.titleHDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast canceren
dc.typeArticle (peer-reviewed)en
oaire.citation.issue34en
oaire.citation.volume40en
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