The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone

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dc.contributor.authorFournier, Pierrick GJ
dc.contributor.authorJuárez, Patricia
dc.contributor.authorJiang, Guanglong
dc.contributor.authorClines, Gregory A.
dc.contributor.authorNiewolna, Maria
dc.contributor.authorKim, Hun Soo
dc.contributor.authorWalton, Holly W.
dc.contributor.authorPeng, C. Xiang Hong
dc.contributor.authorLiu, Yunlong
dc.contributor.authorMohammad, Khalid S.
dc.contributor.authorWells, Clark D.
dc.contributor.authorChirgwin, John M.
dc.contributor.authorGuise, Theresa A.
dc.contributor.departmentDepartment of Medicine, IU School of Medicineen_US
dc.date.accessioned2017-04-12T19:33:50Z
dc.date.available2017-04-12T19:33:50Z
dc.date.issued2015-06-08
dc.description.abstractTransforming growth factor-β (TGF-β) regulates the expression of genes supporting breast cancer cells in bone, but little is known about prostate cancer bone metastases and TGF-β. Our study reveals that the TGFBR1 inhibitor SD208 effectively reduces prostate cancer bone metastases. TGF-β upregulates in prostate cancer cells a set of genes associated with cancer aggressiveness and bone metastases, and the most upregulated gene was PMEPA1. In patients, PMEPA1 expression decreased in metastatic prostate cancer and low Pmepa1 correlated with decreased metastasis-free survival. Only membrane-anchored isoforms of PMEPA1 interacted with R-SMADs and ubiquitin ligases, blocking TGF-β signaling independently of the proteasome. Interrupting this negative feedback loop by PMEPA1 knockdown increased prometastatic gene expression and bone metastases in a mouse prostate cancer model.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationFournier, P. G., Juárez, P., Jiang, G., Clines, G. A., Niewolna, M., Kim, H. S., … Guise, T. A. (2015). The TGFβ Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone. Cancer Cell, 27(6), 809–821. http://doi.org/10.1016/j.ccell.2015.04.009en_US
dc.identifier.issn1878-3686en_US
dc.identifier.urihttps://hdl.handle.net/1805/12245
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.ccell.2015.04.009en_US
dc.relation.journalCancer Cellen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectBone Neoplasmsen_US
dc.subjectsecondaryen_US
dc.subjectMembrane Proteinsen_US
dc.subjectmetabolismen_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectpathologyen_US
dc.subjectTransforming Growth Factor betaen_US
dc.titleThe TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Boneen_US
dc.typeArticleen_US
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