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LIFR-Mediated Tumor Dormancy and Mechanisms of Breast Cancer Dissemination to Bone

dc.creatorClements, Miranda
dc.description.abstractDespite the high prevalence of breast cancer metastasis to bone, there are currently no therapeutic options to cure metastatic disease. This deficit is in part due to the lack in vivo models that recapitulate prolonged tumor latency and limited mechanistic understanding of tumor dormancy and colonization of the bone. We therefore established several novel models of bone colonization (SUM159, D2.0R, bone-tropic MCF7) to study these mechanisms and provide robust methods to detect rare disseminated tumor cells in bone. Using the bone-tropic MCF7 model, our studies identified PREX1 as an important mediator of ER+ tumor cell metastatic potential and dissemination to skeletal sites. Finally, we explored the use of histone deacetylase inhibitors (HDACi) as a means to therapeutically induce tumor dormancy in the bone. Our findings indicate that HDACi enhance promoter acetylation and expression of LIFR while also upregulating other pro-dormancy genes in a LIFR-dependent manner. In breast cancer patients, expression of these dormancy-promoting factors was stimulated with HDACi treatment and inversely correlated with tumor proliferation and metastasis-free survival. Together, these findings offer novel in vivo models to investigate mechanisms underlying tumor dormancy and bone colonization and potential a potential therapeutic avenue to induce and maintain breast cancer cells in a persistent state of dormancy. Approved
dc.subjectHDAC inhibitors
dc.subjecttumor dormancy
dc.subjectbreast cancer
dc.titleLIFR-Mediated Tumor Dormancy and Mechanisms of Breast Cancer Dissemination to Bone
dc.contributor.committeeMemberRachelle W. Johnson
dc.contributor.committeeMemberBarbara Fingleton
dc.contributor.committeeMemberJulie (Sterling) Rhoades
dc.contributor.committeeMemberThomas Stricker
dc.type.materialtext Biology University
dc.contributor.committeeChairAlissa Weaver

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