Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer
Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropr...
Gespeichert in:
Veröffentlicht in: | Journal of personalized medicine 2020-11, Vol.10 (4), p.246 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 4 |
container_start_page | 246 |
container_title | Journal of personalized medicine |
container_volume | 10 |
creator | Ulm, Michael A. Redfern, Tiffany M. Wilson, Ben R. Ponnusamy, Suriyan Asemota, Sarah Blackburn, Patrick W. Wang, Yinan ElNaggar, Adam C. Narayanan, Ramesh |
description | Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation. |
doi_str_mv | 10.3390/jpm10040246 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7712057</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2466036259</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-7f35942b937ac9fa06a4853c91e27afd72124f934a55bbd4f27f550c7db141103</originalsourceid><addsrcrecordid>eNpdkU9rGzEQxUVpqY3rU76AoJdA2Gb0b2VdAsE0ramJL85ZzGq1jty11pF2Df323RBTnM5lBubHY948Qq4YfBPCwO3-eGAAErgsP5ApB60KKXn58WKekHnOexhroTgv4TOZCMFVCcCn5GEVe79LIRbrEH_7mv4KEbOnq0yRPnYn39Lts0949EMfHN1i2vmehkg3J0wBI11idD59IZ8abLOfn_uMPD183y5_FuvNj9Xyfl04sSj7QjdCGckrIzQ60yCUKBdKOMM819jUmjMuGyMkKlVVtWy4bpQCp-uKScZAzMjdm-5xqA6-dj72CVt7TOGA6Y_tMNj3mxie7a47Wa0ZB6VHgeuzQOpeBp97ewjZ-bbF6Lsh2_GPJYiSKzOiX_9D992Q4mjvlVILbcDIkbp5o1zqck6--XcMA_sakb2ISPwFk3yAtg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2465879094</pqid></control><display><type>article</type><title>Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Ulm, Michael A. ; Redfern, Tiffany M. ; Wilson, Ben R. ; Ponnusamy, Suriyan ; Asemota, Sarah ; Blackburn, Patrick W. ; Wang, Yinan ; ElNaggar, Adam C. ; Narayanan, Ramesh</creator><creatorcontrib>Ulm, Michael A. ; Redfern, Tiffany M. ; Wilson, Ben R. ; Ponnusamy, Suriyan ; Asemota, Sarah ; Blackburn, Patrick W. ; Wang, Yinan ; ElNaggar, Adam C. ; Narayanan, Ramesh</creatorcontrib><description>Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.</description><identifier>ISSN: 2075-4426</identifier><identifier>EISSN: 2075-4426</identifier><identifier>DOI: 10.3390/jpm10040246</identifier><identifier>PMID: 33256002</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>AKT protein ; Apoptosis ; Bioinformatics ; Cell culture ; Cell cycle ; Cell growth ; Cell proliferation ; CRISPR ; DNA microarrays ; Drug development ; Drug resistance ; Experiments ; Extracellular matrix ; Gene expression ; Genetic transformation ; Genomes ; ILK protein ; Kinases ; Metastasis ; Ovarian cancer ; Precision medicine ; Proteins ; Reagents ; Software ; Therapeutic applications ; Tumors ; Variance analysis ; Xenografts</subject><ispartof>Journal of personalized medicine, 2020-11, Vol.10 (4), p.246</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-7f35942b937ac9fa06a4853c91e27afd72124f934a55bbd4f27f550c7db141103</citedby><cites>FETCH-LOGICAL-c386t-7f35942b937ac9fa06a4853c91e27afd72124f934a55bbd4f27f550c7db141103</cites><orcidid>0000-0003-0720-2222 ; 0000-0003-3409-583X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712057/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712057/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Ulm, Michael A.</creatorcontrib><creatorcontrib>Redfern, Tiffany M.</creatorcontrib><creatorcontrib>Wilson, Ben R.</creatorcontrib><creatorcontrib>Ponnusamy, Suriyan</creatorcontrib><creatorcontrib>Asemota, Sarah</creatorcontrib><creatorcontrib>Blackburn, Patrick W.</creatorcontrib><creatorcontrib>Wang, Yinan</creatorcontrib><creatorcontrib>ElNaggar, Adam C.</creatorcontrib><creatorcontrib>Narayanan, Ramesh</creatorcontrib><title>Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer</title><title>Journal of personalized medicine</title><description>Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.</description><subject>AKT protein</subject><subject>Apoptosis</subject><subject>Bioinformatics</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>CRISPR</subject><subject>DNA microarrays</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Experiments</subject><subject>Extracellular matrix</subject><subject>Gene expression</subject><subject>Genetic transformation</subject><subject>Genomes</subject><subject>ILK protein</subject><subject>Kinases</subject><subject>Metastasis</subject><subject>Ovarian cancer</subject><subject>Precision medicine</subject><subject>Proteins</subject><subject>Reagents</subject><subject>Software</subject><subject>Therapeutic applications</subject><subject>Tumors</subject><subject>Variance analysis</subject><subject>Xenografts</subject><issn>2075-4426</issn><issn>2075-4426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkU9rGzEQxUVpqY3rU76AoJdA2Gb0b2VdAsE0ramJL85ZzGq1jty11pF2Df323RBTnM5lBubHY948Qq4YfBPCwO3-eGAAErgsP5ApB60KKXn58WKekHnOexhroTgv4TOZCMFVCcCn5GEVe79LIRbrEH_7mv4KEbOnq0yRPnYn39Lts0949EMfHN1i2vmehkg3J0wBI11idD59IZ8abLOfn_uMPD183y5_FuvNj9Xyfl04sSj7QjdCGckrIzQ60yCUKBdKOMM819jUmjMuGyMkKlVVtWy4bpQCp-uKScZAzMjdm-5xqA6-dj72CVt7TOGA6Y_tMNj3mxie7a47Wa0ZB6VHgeuzQOpeBp97ewjZ-bbF6Lsh2_GPJYiSKzOiX_9D992Q4mjvlVILbcDIkbp5o1zqck6--XcMA_sakb2ISPwFk3yAtg</recordid><startdate>20201126</startdate><enddate>20201126</enddate><creator>Ulm, Michael A.</creator><creator>Redfern, Tiffany M.</creator><creator>Wilson, Ben R.</creator><creator>Ponnusamy, Suriyan</creator><creator>Asemota, Sarah</creator><creator>Blackburn, Patrick W.</creator><creator>Wang, Yinan</creator><creator>ElNaggar, Adam C.</creator><creator>Narayanan, Ramesh</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0720-2222</orcidid><orcidid>https://orcid.org/0000-0003-3409-583X</orcidid></search><sort><creationdate>20201126</creationdate><title>Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer</title><author>Ulm, Michael A. ; Redfern, Tiffany M. ; Wilson, Ben R. ; Ponnusamy, Suriyan ; Asemota, Sarah ; Blackburn, Patrick W. ; Wang, Yinan ; ElNaggar, Adam C. ; Narayanan, Ramesh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-7f35942b937ac9fa06a4853c91e27afd72124f934a55bbd4f27f550c7db141103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>AKT protein</topic><topic>Apoptosis</topic><topic>Bioinformatics</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>CRISPR</topic><topic>DNA microarrays</topic><topic>Drug development</topic><topic>Drug resistance</topic><topic>Experiments</topic><topic>Extracellular matrix</topic><topic>Gene expression</topic><topic>Genetic transformation</topic><topic>Genomes</topic><topic>ILK protein</topic><topic>Kinases</topic><topic>Metastasis</topic><topic>Ovarian cancer</topic><topic>Precision medicine</topic><topic>Proteins</topic><topic>Reagents</topic><topic>Software</topic><topic>Therapeutic applications</topic><topic>Tumors</topic><topic>Variance analysis</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ulm, Michael A.</creatorcontrib><creatorcontrib>Redfern, Tiffany M.</creatorcontrib><creatorcontrib>Wilson, Ben R.</creatorcontrib><creatorcontrib>Ponnusamy, Suriyan</creatorcontrib><creatorcontrib>Asemota, Sarah</creatorcontrib><creatorcontrib>Blackburn, Patrick W.</creatorcontrib><creatorcontrib>Wang, Yinan</creatorcontrib><creatorcontrib>ElNaggar, Adam C.</creatorcontrib><creatorcontrib>Narayanan, Ramesh</creatorcontrib><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of personalized medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ulm, Michael A.</au><au>Redfern, Tiffany M.</au><au>Wilson, Ben R.</au><au>Ponnusamy, Suriyan</au><au>Asemota, Sarah</au><au>Blackburn, Patrick W.</au><au>Wang, Yinan</au><au>ElNaggar, Adam C.</au><au>Narayanan, Ramesh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer</atitle><jtitle>Journal of personalized medicine</jtitle><date>2020-11-26</date><risdate>2020</risdate><volume>10</volume><issue>4</issue><spage>246</spage><pages>246-</pages><issn>2075-4426</issn><eissn>2075-4426</eissn><abstract>Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>33256002</pmid><doi>10.3390/jpm10040246</doi><orcidid>https://orcid.org/0000-0003-0720-2222</orcidid><orcidid>https://orcid.org/0000-0003-3409-583X</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2075-4426 |
ispartof | Journal of personalized medicine, 2020-11, Vol.10 (4), p.246 |
issn | 2075-4426 2075-4426 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7712057 |
source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
subjects | AKT protein Apoptosis Bioinformatics Cell culture Cell cycle Cell growth Cell proliferation CRISPR DNA microarrays Drug development Drug resistance Experiments Extracellular matrix Gene expression Genetic transformation Genomes ILK protein Kinases Metastasis Ovarian cancer Precision medicine Proteins Reagents Software Therapeutic applications Tumors Variance analysis Xenografts |
title | Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T05%3A32%3A38IST&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=Integrin-Linked%20Kinase%20Is%20a%20Novel%20Therapeutic%20Target%20in%20Ovarian%20Cancer&rft.jtitle=Journal%20of%20personalized%20medicine&rft.au=Ulm,%20Michael%20A.&rft.date=2020-11-26&rft.volume=10&rft.issue=4&rft.spage=246&rft.pages=246-&rft.issn=2075-4426&rft.eissn=2075-4426&rft_id=info:doi/10.3390/jpm10040246&rft_dat=%3Cproquest_pubme%3E2466036259%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=2465879094&rft_id=info:pmid/33256002&rfr_iscdi=true |