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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer letters 2019-04, Vol.448, p.182-196
Hauptverfasser: 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
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 &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; 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