Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer

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dc.contributor.authorChen, Wei-Yu
dc.contributor.authorTsai, Yuan-Chin
dc.contributor.authorYeh, Hsiu-Lien
dc.contributor.authorSuau, Florent
dc.contributor.authorJiang, Kuo-Ching
dc.contributor.authorShao, Ai-Ning
dc.contributor.authorHuang, Jiaoti
dc.date.accessioned2024-04-24T17:11:52Z
dc.date.available2024-04-24T17:11:52Z
dc.date.issued2017
dc.departmentDicle Üniversitesien_US
dc.description.abstractAndrogen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-beta (TGF beta)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI. ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells. Knockdown of TGFBI suppressed migration and proliferation in cultured cells and reduced prostate tumor growth and brain and bone metastasis in xenograft models, extending the survival of tumor-bearing mice. Analysis of prostate tissue samples collected before and after ADT from the same patients showed that ADT reduced the nuclear abundance of SPDEF and increased the production of TGFBI. Our findings suggest that induction of TGFBI promotes prostate cancer growth and metastasis and can be caused by dysregulation or therapeutic inhibition of AR signaling.en_US
dc.description.sponsorshipMinistry of Science and Technology of Taiwan [MOST 106-2320-B-038-057, MOST 104-2320-B-038-055-MY3, MOST 104-2314-B-038-045-MY3]; National Health Research Institutes of Taiwan [NHRI-EX106-10308BC]; Health and Welfare Surcharge of Tobacco Products [MOHW106-TDU-B-212-144001]en_US
dc.description.sponsorshipThis work was jointly supported by grants from the Ministry of Science and Technology of Taiwan to W.-Y.C. (MOST 106-2320-B-038-057), Y.-C.T. (MOST 104-2320-B-038-055-MY3), and Y.-N.L. (MOST 104-2314-B-038-045-MY3); by the National Health Research Institutes of Taiwan to Y.-N.L. (NHRI-EX106-10308BC), and by the Health and Welfare Surcharge of Tobacco Products to Y.-N.L. (MOHW106-TDU-B-212-144001).en_US
dc.identifier.doi10.1126/scisignal.aam6826
dc.identifier.issn1945-0877
dc.identifier.issn1937-9145
dc.identifier.issue492en_US
dc.identifier.pmid28811384en_US
dc.identifier.scopus2-s2.0-85027719162en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1126/scisignal.aam6826
dc.identifier.urihttps://hdl.handle.net/11468/17754
dc.identifier.volume10en_US
dc.identifier.wosWOS:000407598900002
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherAmer Assoc Advancement Scienceen_US
dc.relation.ispartofScience Signalingen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keyword]en_US
dc.titleLoss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate canceren_US
dc.typeArticleen_US

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