Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer
This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mous...
Gespeichert in:
Veröffentlicht in: | Cancer letters 2019-04, Vol.448, p.182-196 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 196 |
---|---|
container_issue | |
container_start_page | 182 |
container_title | Cancer letters |
container_volume | 448 |
creator | Nikhil, Kumar Chang, Lei Viccaro, Keith Jacobsen, Max McGuire, Callista Satapathy, Shakti R. Tandiary, Michael Broman, Meaghan M. Cresswell, Gregory He, Yizhou J. Sandusky, George E. Ratliff, Timothy L. Chowdhury, Dipanjan Shah, Kavita |
description | This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients.
•LIMK2 was identified as a disease-specific target in CRPC.•We show that LIMK2 is upregulated in castrated prostates due to increased hypoxia.•Inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice.•TWIST1 was identified a direct target of LIMK2.•LIMK2 inhibitor shows very high synergy with docetaxel. |
doi_str_mv | 10.1016/j.canlet.2019.01.035 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7079209</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0304383519300552</els_id><sourcerecordid>2188915990</sourcerecordid><originalsourceid>FETCH-LOGICAL-c491t-a55eb7c2274c5258edd35e885409b6dd7dc84e85d5b413aa2e093fc550d4b7fa3</originalsourceid><addsrcrecordid>eNp9kUGLFDEQhYMo7jj6D0QavHjpttJJJslFkGV1B0e8KB5DOqnezdCTHpP0gv_eLLPuqgdPKaivXurVI-QlhY4C3bzdd87GCUvXA9Ud0A6YeERWVMm-lVrBY7ICBrxliokz8iznPQAILsVTcsZA0g3bwIp833qMJYzB2RLm2Mxjs9t-_tQ3Nje2KdeY7BGXElxTbLrC0oTYOJtLOuEJc8jFxtIc01yLgrUbHabn5Mlop4wv7t41-fbh4uv5Zbv78nF7_n7XOq5paa0QOEjX95I70QuF3jOBSgkOeth4L71THJXwYuCUWdsjaDY6IcDzQY6Wrcm7k-5xGQ7oXTWT7GSOKRxs-mlmG8zfnRiuzdV8YyRI3VexNXlzJ5DmHwvmYg4hO5wmG3Fesump1HUzKUVFX_-D7uclxWqvUkppKrSGSvET5epFcsLxfhkK5jY5szen5MxtcgaoqcnVsVd_Grkf-h3Vg1Os57wJmEx2AeutfUjoivFz-P8PvwBemq0F</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2188915990</pqid></control><display><type>article</type><title>Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Nikhil, Kumar ; Chang, Lei ; Viccaro, Keith ; Jacobsen, Max ; McGuire, Callista ; Satapathy, Shakti R. ; Tandiary, Michael ; Broman, Meaghan M. ; Cresswell, Gregory ; He, Yizhou J. ; Sandusky, George E. ; Ratliff, Timothy L. ; Chowdhury, Dipanjan ; Shah, Kavita</creator><creatorcontrib>Nikhil, Kumar ; Chang, Lei ; Viccaro, Keith ; Jacobsen, Max ; McGuire, Callista ; Satapathy, Shakti R. ; Tandiary, Michael ; Broman, Meaghan M. ; Cresswell, Gregory ; He, Yizhou J. ; Sandusky, George E. ; Ratliff, Timothy L. ; Chowdhury, Dipanjan ; Shah, Kavita</creatorcontrib><description>This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients.
•LIMK2 was identified as a disease-specific target in CRPC.•We show that LIMK2 is upregulated in castrated prostates due to increased hypoxia.•Inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice.•TWIST1 was identified a direct target of LIMK2.•LIMK2 inhibitor shows very high synergy with docetaxel.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2019.01.035</identifier><identifier>PMID: 30716360</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Analysis of Variance ; Animals ; Cancer therapies ; Castration ; Castration resistant prostate cancer ; Chemotherapy ; CRISPR ; Experiments ; Feedback ; Hypoxia ; Hypoxia - metabolism ; Immunoglobulins ; Kinases ; Lim Kinases - metabolism ; LIMK2 ; Male ; Malignancy ; Medical research ; Metastasis ; Mice ; Molecular Targeted Therapy - methods ; mRNA ; Phosphorylation ; Plasmids ; Prostate cancer ; Prostatic Neoplasms, Castration-Resistant - metabolism ; Prostatic Neoplasms, Castration-Resistant - pathology ; Proteins ; RNA, Mitochondrial - metabolism ; Software ; Therapeutic applications ; Toxicity ; Tumorigenesis ; Tumors ; Twist-Related Protein 1 ; TWIST1 ; Ubiquitin</subject><ispartof>Cancer letters, 2019-04, Vol.448, p.182-196</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Limited Apr 28, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-a55eb7c2274c5258edd35e885409b6dd7dc84e85d5b413aa2e093fc550d4b7fa3</citedby><cites>FETCH-LOGICAL-c491t-a55eb7c2274c5258edd35e885409b6dd7dc84e85d5b413aa2e093fc550d4b7fa3</cites><orcidid>0000-0002-1396-7275 ; 0000-0002-0451-1305</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2019.01.035$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30716360$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nikhil, Kumar</creatorcontrib><creatorcontrib>Chang, Lei</creatorcontrib><creatorcontrib>Viccaro, Keith</creatorcontrib><creatorcontrib>Jacobsen, Max</creatorcontrib><creatorcontrib>McGuire, Callista</creatorcontrib><creatorcontrib>Satapathy, Shakti R.</creatorcontrib><creatorcontrib>Tandiary, Michael</creatorcontrib><creatorcontrib>Broman, Meaghan M.</creatorcontrib><creatorcontrib>Cresswell, Gregory</creatorcontrib><creatorcontrib>He, Yizhou J.</creatorcontrib><creatorcontrib>Sandusky, George E.</creatorcontrib><creatorcontrib>Ratliff, Timothy L.</creatorcontrib><creatorcontrib>Chowdhury, Dipanjan</creatorcontrib><creatorcontrib>Shah, Kavita</creatorcontrib><title>Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients.
•LIMK2 was identified as a disease-specific target in CRPC.•We show that LIMK2 is upregulated in castrated prostates due to increased hypoxia.•Inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice.•TWIST1 was identified a direct target of LIMK2.•LIMK2 inhibitor shows very high synergy with docetaxel.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Cancer therapies</subject><subject>Castration</subject><subject>Castration resistant prostate cancer</subject><subject>Chemotherapy</subject><subject>CRISPR</subject><subject>Experiments</subject><subject>Feedback</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Immunoglobulins</subject><subject>Kinases</subject><subject>Lim Kinases - metabolism</subject><subject>LIMK2</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Molecular Targeted Therapy - methods</subject><subject>mRNA</subject><subject>Phosphorylation</subject><subject>Plasmids</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms, Castration-Resistant - metabolism</subject><subject>Prostatic Neoplasms, Castration-Resistant - pathology</subject><subject>Proteins</subject><subject>RNA, Mitochondrial - metabolism</subject><subject>Software</subject><subject>Therapeutic applications</subject><subject>Toxicity</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Twist-Related Protein 1</subject><subject>TWIST1</subject><subject>Ubiquitin</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUGLFDEQhYMo7jj6D0QavHjpttJJJslFkGV1B0e8KB5DOqnezdCTHpP0gv_eLLPuqgdPKaivXurVI-QlhY4C3bzdd87GCUvXA9Ud0A6YeERWVMm-lVrBY7ICBrxliokz8iznPQAILsVTcsZA0g3bwIp833qMJYzB2RLm2Mxjs9t-_tQ3Nje2KdeY7BGXElxTbLrC0oTYOJtLOuEJc8jFxtIc01yLgrUbHabn5Mlop4wv7t41-fbh4uv5Zbv78nF7_n7XOq5paa0QOEjX95I70QuF3jOBSgkOeth4L71THJXwYuCUWdsjaDY6IcDzQY6Wrcm7k-5xGQ7oXTWT7GSOKRxs-mlmG8zfnRiuzdV8YyRI3VexNXlzJ5DmHwvmYg4hO5wmG3Fesump1HUzKUVFX_-D7uclxWqvUkppKrSGSvET5epFcsLxfhkK5jY5szen5MxtcgaoqcnVsVd_Grkf-h3Vg1Os57wJmEx2AeutfUjoivFz-P8PvwBemq0F</recordid><startdate>20190428</startdate><enddate>20190428</enddate><creator>Nikhil, Kumar</creator><creator>Chang, Lei</creator><creator>Viccaro, Keith</creator><creator>Jacobsen, Max</creator><creator>McGuire, Callista</creator><creator>Satapathy, Shakti R.</creator><creator>Tandiary, Michael</creator><creator>Broman, Meaghan M.</creator><creator>Cresswell, Gregory</creator><creator>He, Yizhou J.</creator><creator>Sandusky, George E.</creator><creator>Ratliff, Timothy L.</creator><creator>Chowdhury, Dipanjan</creator><creator>Shah, Kavita</creator><general>Elsevier B.V</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1396-7275</orcidid><orcidid>https://orcid.org/0000-0002-0451-1305</orcidid></search><sort><creationdate>20190428</creationdate><title>Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer</title><author>Nikhil, Kumar ; Chang, Lei ; Viccaro, Keith ; Jacobsen, Max ; McGuire, Callista ; Satapathy, Shakti R. ; Tandiary, Michael ; Broman, Meaghan M. ; Cresswell, Gregory ; He, Yizhou J. ; Sandusky, George E. ; Ratliff, Timothy L. ; Chowdhury, Dipanjan ; Shah, Kavita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-a55eb7c2274c5258edd35e885409b6dd7dc84e85d5b413aa2e093fc550d4b7fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Cancer therapies</topic><topic>Castration</topic><topic>Castration resistant prostate cancer</topic><topic>Chemotherapy</topic><topic>CRISPR</topic><topic>Experiments</topic><topic>Feedback</topic><topic>Hypoxia</topic><topic>Hypoxia - metabolism</topic><topic>Immunoglobulins</topic><topic>Kinases</topic><topic>Lim Kinases - metabolism</topic><topic>LIMK2</topic><topic>Male</topic><topic>Malignancy</topic><topic>Medical research</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Molecular Targeted Therapy - methods</topic><topic>mRNA</topic><topic>Phosphorylation</topic><topic>Plasmids</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms, Castration-Resistant - metabolism</topic><topic>Prostatic Neoplasms, Castration-Resistant - pathology</topic><topic>Proteins</topic><topic>RNA, Mitochondrial - metabolism</topic><topic>Software</topic><topic>Therapeutic applications</topic><topic>Toxicity</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Twist-Related Protein 1</topic><topic>TWIST1</topic><topic>Ubiquitin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nikhil, Kumar</creatorcontrib><creatorcontrib>Chang, Lei</creatorcontrib><creatorcontrib>Viccaro, Keith</creatorcontrib><creatorcontrib>Jacobsen, Max</creatorcontrib><creatorcontrib>McGuire, Callista</creatorcontrib><creatorcontrib>Satapathy, Shakti R.</creatorcontrib><creatorcontrib>Tandiary, Michael</creatorcontrib><creatorcontrib>Broman, Meaghan M.</creatorcontrib><creatorcontrib>Cresswell, Gregory</creatorcontrib><creatorcontrib>He, Yizhou J.</creatorcontrib><creatorcontrib>Sandusky, George E.</creatorcontrib><creatorcontrib>Ratliff, Timothy L.</creatorcontrib><creatorcontrib>Chowdhury, Dipanjan</creatorcontrib><creatorcontrib>Shah, Kavita</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nikhil, Kumar</au><au>Chang, Lei</au><au>Viccaro, Keith</au><au>Jacobsen, Max</au><au>McGuire, Callista</au><au>Satapathy, Shakti R.</au><au>Tandiary, Michael</au><au>Broman, Meaghan M.</au><au>Cresswell, Gregory</au><au>He, Yizhou J.</au><au>Sandusky, George E.</au><au>Ratliff, Timothy L.</au><au>Chowdhury, Dipanjan</au><au>Shah, Kavita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2019-04-28</date><risdate>2019</risdate><volume>448</volume><spage>182</spage><epage>196</epage><pages>182-196</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients.
•LIMK2 was identified as a disease-specific target in CRPC.•We show that LIMK2 is upregulated in castrated prostates due to increased hypoxia.•Inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice.•TWIST1 was identified a direct target of LIMK2.•LIMK2 inhibitor shows very high synergy with docetaxel.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30716360</pmid><doi>10.1016/j.canlet.2019.01.035</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1396-7275</orcidid><orcidid>https://orcid.org/0000-0002-0451-1305</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0304-3835 |
ispartof | Cancer letters, 2019-04, Vol.448, p.182-196 |
issn | 0304-3835 1872-7980 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7079209 |
source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
subjects | Analysis of Variance Animals Cancer therapies Castration Castration resistant prostate cancer Chemotherapy CRISPR Experiments Feedback Hypoxia Hypoxia - metabolism Immunoglobulins Kinases Lim Kinases - metabolism LIMK2 Male Malignancy Medical research Metastasis Mice Molecular Targeted Therapy - methods mRNA Phosphorylation Plasmids Prostate cancer Prostatic Neoplasms, Castration-Resistant - metabolism Prostatic Neoplasms, Castration-Resistant - pathology Proteins RNA, Mitochondrial - metabolism Software Therapeutic applications Toxicity Tumorigenesis Tumors Twist-Related Protein 1 TWIST1 Ubiquitin |
title | Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T19%3A45%3A26IST&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=Identification%20of%20LIMK2%20as%20a%20therapeutic%20target%20in%20castration%20resistant%20prostate%20cancer&rft.jtitle=Cancer%20letters&rft.au=Nikhil,%20Kumar&rft.date=2019-04-28&rft.volume=448&rft.spage=182&rft.epage=196&rft.pages=182-196&rft.issn=0304-3835&rft.eissn=1872-7980&rft_id=info:doi/10.1016/j.canlet.2019.01.035&rft_dat=%3Cproquest_pubme%3E2188915990%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2188915990&rft_id=info:pmid/30716360&rft_els_id=S0304383519300552&rfr_iscdi=true |