Cited 22 times in
Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis
DC Field | Value | Language |
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dc.contributor.author | 한현호 | - |
dc.date.accessioned | 2022-08-23T00:12:46Z | - |
dc.date.available | 2022-08-23T00:12:46Z | - |
dc.date.issued | 2022-04 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/189314 | - |
dc.description.abstract | Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity. AR blockade with enzalutamide induces (1) transcriptional silencing of TP53 and hence dedifferentiation to a hybrid epithelial and mesenchymal and stem-like state and (2) inhibition of BMP signaling, which promotes resistance to AR inhibition. Enzalutamide-tolerant LNCaP cells re-enter the cell cycle in response to neuregulin and generate metastasis in mice. Combined inhibition of HER2/3 and AR or mTORC1 exhibits efficacy in models of ARPC and MSPC or MSPC, respectively. These results define MSPC, trace its origin to therapy-induced lineage plasticity, and reveal its sensitivity to HER2/3 inhibition. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Cell Press | - |
dc.relation.isPartOf | CELL REPORTS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antineoplastic Agents* / pharmacology | - |
dc.subject.MESH | Benzamides | - |
dc.subject.MESH | Carcinoma, Neuroendocrine | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Plasticity / drug effects | - |
dc.subject.MESH | Cell Plasticity / physiology | - |
dc.subject.MESH | Drug Resistance, Neoplasm | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Neoplastic Stem Cells / drug effects | - |
dc.subject.MESH | Neoplastic Stem Cells / metabolism | - |
dc.subject.MESH | Nitriles | - |
dc.subject.MESH | Phenylthiohydantoin | - |
dc.subject.MESH | Prostatic Neoplasms, Castration-Resistant* / drug therapy | - |
dc.subject.MESH | Prostatic Neoplasms, Castration-Resistant* / genetics | - |
dc.subject.MESH | Prostatic Neoplasms, Castration-Resistant* / metabolism | - |
dc.subject.MESH | Receptors, Androgen / drug effects | - |
dc.subject.MESH | Receptors, Androgen / metabolism | - |
dc.subject.MESH | Signal Transduction* | - |
dc.subject.MESH | Tumor Microenvironment / drug effects | - |
dc.subject.MESH | Tumor Microenvironment / physiology | - |
dc.title | Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Urology (비뇨의학교실) | - |
dc.contributor.googleauthor | Hyunho Han | - |
dc.contributor.googleauthor | Yan Wang | - |
dc.contributor.googleauthor | Josue Curto | - |
dc.contributor.googleauthor | Sreeharsha Gurrapu | - |
dc.contributor.googleauthor | Sara Laudato | - |
dc.contributor.googleauthor | Alekya Rumandla | - |
dc.contributor.googleauthor | Goutam Chakraborty | - |
dc.contributor.googleauthor | Xiaobo Wang | - |
dc.contributor.googleauthor | Hong Chen | - |
dc.contributor.googleauthor | Yan Jiang | - |
dc.contributor.googleauthor | Dhiraj Kumar | - |
dc.contributor.googleauthor | Emily G Caggiano | - |
dc.contributor.googleauthor | Monica Capogiri | - |
dc.contributor.googleauthor | Boyu Zhang | - |
dc.contributor.googleauthor | Yan Ji | - |
dc.contributor.googleauthor | Sankar N Maity | - |
dc.contributor.googleauthor | Min Hu | - |
dc.contributor.googleauthor | Shanshan Bai | - |
dc.contributor.googleauthor | Ana M Aparicio | - |
dc.contributor.googleauthor | Eleni Efstathiou | - |
dc.contributor.googleauthor | Christopher J Logothetis | - |
dc.contributor.googleauthor | Nicholas Navin | - |
dc.contributor.googleauthor | Nora M Navone | - |
dc.contributor.googleauthor | Yu Chen | - |
dc.contributor.googleauthor | Filippo G Giancotti | - |
dc.identifier.doi | 10.1016/j.celrep.2022.110595 | - |
dc.contributor.localId | A04333 | - |
dc.relation.journalcode | J00488 | - |
dc.identifier.eissn | 2211-1247 | - |
dc.identifier.pmid | 35385726 | - |
dc.subject.keyword | BMP-SMAD signaling | - |
dc.subject.keyword | CP: Cancer | - |
dc.subject.keyword | TP53 | - |
dc.subject.keyword | androgen receptor signaling | - |
dc.subject.keyword | prostate cancer | - |
dc.contributor.alternativeName | Han, Hyun Ho | - |
dc.contributor.affiliatedAuthor | 한현호 | - |
dc.citation.volume | 39 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 110595 | - |
dc.identifier.bibliographicCitation | CELL REPORTS, Vol.39(1) : 110595, 2022-04 | - |
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