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ERG induces taxane resistance in castration-resistant prostate cancer
Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in...
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| Published in: | Nature communications 2014-11, Vol.5 (1), p.5548-5548, Article 5548 |
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| creator | Galletti, Giuseppe Matov, Alexandre Beltran, Himisha Fontugne, Jacqueline Miguel Mosquera, Juan Cheung, Cynthia MacDonald, Theresa Y. Sung, Matthew O’Toole, Sandra Kench, James G. Suk Chae, Sung Kimovski, Dragi Tagawa, Scott T. Nanus, David M. Rubin, Mark A. Horvath, Lisa G. Giannakakou, Paraskevi Rickman, David S. |
| description | Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in
in vitro
and
in vivo
models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.
Metastatic castration-resistant prostate cancer is treated with the microtubule-stabilizing drugs taxanes, but resistance ultimately develops. Here Galletti
et al.
show that ERG, a transcription factor commonly overexpressed in prostate cancers, confers taxane resistance by binding to soluble tubulin. |
| doi_str_mv | 10.1038/ncomms6548 |
| format | article |
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in vitro
and
in vivo
models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.
Metastatic castration-resistant prostate cancer is treated with the microtubule-stabilizing drugs taxanes, but resistance ultimately develops. Here Galletti
et al.
show that ERG, a transcription factor commonly overexpressed in prostate cancers, confers taxane resistance by binding to soluble tubulin.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms6548</identifier><identifier>PMID: 25420520</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 14 ; 14/19 ; 59 ; 59/5 ; 631/67/1059/2326 ; 631/67/1059/99 ; 631/67/589/466 ; 64/60 ; Antineoplastic Agents - administration & dosage ; Cancer therapies ; Cell Line, Tumor ; Chemotherapy ; Cohort Studies ; Cooperation ; Drug dosages ; Drug resistance ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic - drug effects ; Humanities and Social Sciences ; Humans ; Male ; Metastasis ; multidisciplinary ; Oncology ; Polymerization ; Polymers ; Prostate cancer ; Prostatic Neoplasms, Castration-Resistant - drug therapy ; Prostatic Neoplasms, Castration-Resistant - genetics ; Prostatic Neoplasms, Castration-Resistant - metabolism ; Science ; Science (multidisciplinary) ; Taxoids - administration & dosage ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcriptional Regulator ERG ; Tubulin - genetics ; Tubulin - metabolism</subject><ispartof>Nature communications, 2014-11, Vol.5 (1), p.5548-5548, Article 5548</ispartof><rights>The Author(s) 2014</rights><rights>Copyright Nature Publishing Group Nov 2014</rights><rights>Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-ce813ccfdc7278f61ae23855f63dd4a5e063d7771d0997f0fc4a95c8e81e7d6c3</citedby><cites>FETCH-LOGICAL-c442t-ce813ccfdc7278f61ae23855f63dd4a5e063d7771d0997f0fc4a95c8e81e7d6c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1627716036/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1627716036?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,75096</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25420520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Galletti, Giuseppe</creatorcontrib><creatorcontrib>Matov, Alexandre</creatorcontrib><creatorcontrib>Beltran, Himisha</creatorcontrib><creatorcontrib>Fontugne, Jacqueline</creatorcontrib><creatorcontrib>Miguel Mosquera, Juan</creatorcontrib><creatorcontrib>Cheung, Cynthia</creatorcontrib><creatorcontrib>MacDonald, Theresa Y.</creatorcontrib><creatorcontrib>Sung, Matthew</creatorcontrib><creatorcontrib>O’Toole, Sandra</creatorcontrib><creatorcontrib>Kench, James G.</creatorcontrib><creatorcontrib>Suk Chae, Sung</creatorcontrib><creatorcontrib>Kimovski, Dragi</creatorcontrib><creatorcontrib>Tagawa, Scott T.</creatorcontrib><creatorcontrib>Nanus, David M.</creatorcontrib><creatorcontrib>Rubin, Mark A.</creatorcontrib><creatorcontrib>Horvath, Lisa G.</creatorcontrib><creatorcontrib>Giannakakou, Paraskevi</creatorcontrib><creatorcontrib>Rickman, David S.</creatorcontrib><title>ERG induces taxane resistance in castration-resistant prostate cancer</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in
in vitro
and
in vivo
models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.
Metastatic castration-resistant prostate cancer is treated with the microtubule-stabilizing drugs taxanes, but resistance ultimately develops. Here Galletti
et al.
show that ERG, a transcription factor commonly overexpressed in prostate cancers, confers taxane resistance by binding to soluble tubulin.</description><subject>13/2</subject><subject>14</subject><subject>14/19</subject><subject>59</subject><subject>59/5</subject><subject>631/67/1059/2326</subject><subject>631/67/1059/99</subject><subject>631/67/589/466</subject><subject>64/60</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Cohort Studies</subject><subject>Cooperation</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Male</subject><subject>Metastasis</subject><subject>multidisciplinary</subject><subject>Oncology</subject><subject>Polymerization</subject><subject>Polymers</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms, Castration-Resistant - drug therapy</subject><subject>Prostatic Neoplasms, Castration-Resistant - genetics</subject><subject>Prostatic Neoplasms, Castration-Resistant - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Taxoids - administration & dosage</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcriptional Regulator ERG</subject><subject>Tubulin - genetics</subject><subject>Tubulin - metabolism</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNplkV9LwzAUxYMobsy9-AGk4Iso1SRNm-xFkDGnIAiizyGm6exok5mkot_eO_bHqXnJhfPLuefmInRM8CXBmbiy2rVtKHIm9lCfYkZSwmm2v1P30DCEOYaTjYhg7BD1aM4ozinuo8nkaZrUtuy0CUlUn8qaxJtQh6isNqAkWoXoVaydTTdCTBbeQRENqID5I3RQqSaY4foeoJfbyfP4Ln14nN6Pbx5SzRiNqTaCZFpXpeaUi6ogytBM5HlVZGXJVG4wFJxzUuLRiFe40kyNci3gmeFlobMBul75LrrX1pTaWIjWyIWvW-W_pFO1_K3Y-k3O3IdklLECMzA4Wxt4996ZEGVbB22aBuZ2XZCkoIIyQqgA9PQPOnedtzDekoKQBc4KoM5XlIYfCd5U2zAEy-WC5M-CAD7Zjb9FN-sA4GIFBJDszPidnv_tvgEtF5w6</recordid><startdate>20141125</startdate><enddate>20141125</enddate><creator>Galletti, Giuseppe</creator><creator>Matov, Alexandre</creator><creator>Beltran, Himisha</creator><creator>Fontugne, Jacqueline</creator><creator>Miguel Mosquera, Juan</creator><creator>Cheung, Cynthia</creator><creator>MacDonald, Theresa Y.</creator><creator>Sung, Matthew</creator><creator>O’Toole, Sandra</creator><creator>Kench, James G.</creator><creator>Suk Chae, Sung</creator><creator>Kimovski, Dragi</creator><creator>Tagawa, Scott T.</creator><creator>Nanus, David M.</creator><creator>Rubin, Mark A.</creator><creator>Horvath, Lisa G.</creator><creator>Giannakakou, Paraskevi</creator><creator>Rickman, David S.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Pub. 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Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in
in vitro
and
in vivo
models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.
Metastatic castration-resistant prostate cancer is treated with the microtubule-stabilizing drugs taxanes, but resistance ultimately develops. Here Galletti
et al.
show that ERG, a transcription factor commonly overexpressed in prostate cancers, confers taxane resistance by binding to soluble tubulin.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25420520</pmid><doi>10.1038/ncomms6548</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-1723 |
| ispartof | Nature communications, 2014-11, Vol.5 (1), p.5548-5548, Article 5548 |
| issn | 2041-1723 2041-1723 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4244604 |
| source | Nature_系列刊; ProQuest - Publicly Available Content Database; PubMed Central; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 13/2 14 14/19 59 59/5 631/67/1059/2326 631/67/1059/99 631/67/589/466 64/60 Antineoplastic Agents - administration & dosage Cancer therapies Cell Line, Tumor Chemotherapy Cohort Studies Cooperation Drug dosages Drug resistance Drug Resistance, Neoplasm Gene Expression Regulation, Neoplastic - drug effects Humanities and Social Sciences Humans Male Metastasis multidisciplinary Oncology Polymerization Polymers Prostate cancer Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - genetics Prostatic Neoplasms, Castration-Resistant - metabolism Science Science (multidisciplinary) Taxoids - administration & dosage Trans-Activators - genetics Trans-Activators - metabolism Transcriptional Regulator ERG Tubulin - genetics Tubulin - metabolism |
| title | ERG induces taxane resistance in castration-resistant prostate cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-23T13%3A26%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ERG%20induces%20taxane%20resistance%20in%20castration-resistant%20prostate%20cancer&rft.jtitle=Nature%20communications&rft.au=Galletti,%20Giuseppe&rft.date=2014-11-25&rft.volume=5&rft.issue=1&rft.spage=5548&rft.epage=5548&rft.pages=5548-5548&rft.artnum=5548&rft.issn=2041-1723&rft.eissn=2041-1723&rft_id=info:doi/10.1038/ncomms6548&rft_dat=%3Cproquest_pubme%3E1628241128%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c442t-ce813ccfdc7278f61ae23855f63dd4a5e063d7771d0997f0fc4a95c8e81e7d6c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1627716036&rft_id=info:pmid/25420520&rfr_iscdi=true |