Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling

Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ova...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Human cell : official journal of Human Cell Research Society 2020-07, Vol.33 (3), p.768-779
Hauptverfasser: Liu, Xiaohan, Zhang, Jing, Duan, Zhaoning, Feng, Xiushan, Yu, Yang, He, Min, Tang, Liangdan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 779
container_issue 3
container_start_page 768
container_title Human cell : official journal of Human Cell Research Society
container_volume 33
creator Liu, Xiaohan
Zhang, Jing
Duan, Zhaoning
Feng, Xiushan
Yu, Yang
He, Min
Tang, Liangdan
description Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ovarian tissues, and the up-regulated Nck1 expression is associated with the aggressiveness of OC and shorter overall and disease-free survival in this population. Higher Nck1 expression was an independent risk factor for poor prognosis of OC. Furthermore, Nck1 silencing by short hairpin RNA (shRNA) technology significantly inhibited the proliferation, migration and invasion of OC cells in vitro and the growth and metastasis of implanted OC tumors in vivo. Human kinase phosphorylation array indicated that Nck1 silencing significantly reduced the relative levels of 11 kinase expression and phosphorylation in OC cells, particularly for decreased levels of p70S6 kinase (p70S6K) and protein kinase B (AKT) expression in SKOV3 cells. Actually, Nck1 silencing significantly decreased PI3K and AKT expression, and reduced AKT and p70S6K phosphorylation while Nck1 over-expression had opposite effects in OC cells. Therefore, our data indicate that Nck1 promotes the progression of OC by enhancing the PI3k/AKT/p70S6K signaling in OC. Our findings suggest that Nck1 expression may be valuable for evaluating the prognosis of OC and as a target for design of new therapies for OC.
doi_str_mv 10.1007/s13577-020-00344-8
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2377346960</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2377346960</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-65140f2bbbc6c8f1c43eae1507d3ac8ce19dc91f4f5a7cf0e4a2226932e56d043</originalsourceid><addsrcrecordid>eNp9kElPwzAQhS0Eomx_gAOKxIVL6HhPjgixqQiQKEdkOY4TUpq42A1S_z1uyyYOnGZG8703o4fQIYZTDCCHAVMuZQoEUgDKWJptoB0sWZ6ClGzzVz9AuyFMABhngmyjASVYCC74Dnq-M684mXnXurkNyfzFLofa2xAa1yWuSty79o3uEqO9aTrX6qRYJLZ70V0c65Xi4YaOhmej8XAm4VGMktDUnZ7G7T7aqvQ02IPPuoeeLi_G59fp7f3VzfnZbWqo5PNUcMygIkVRGGGyChtGrbaYgyypNpmxOC9NjitWcS1NBZZpQojIKbFclMDoHjpZ-8bf33ob5qptgrHTqe6s64MiVErKRC4gosd_0InrfXw3UgxnkjPKlxRZU8a7ELyt1Mw3rfYLhUEtw1fr8FUMX63CV1kUHX1a90Vry2_JV9oRoGsgxFVXW_9z-x_bD-mVjeQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2418754350</pqid></control><display><type>article</type><title>Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Liu, Xiaohan ; Zhang, Jing ; Duan, Zhaoning ; Feng, Xiushan ; Yu, Yang ; He, Min ; Tang, Liangdan</creator><creatorcontrib>Liu, Xiaohan ; Zhang, Jing ; Duan, Zhaoning ; Feng, Xiushan ; Yu, Yang ; He, Min ; Tang, Liangdan</creatorcontrib><description>Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ovarian tissues, and the up-regulated Nck1 expression is associated with the aggressiveness of OC and shorter overall and disease-free survival in this population. Higher Nck1 expression was an independent risk factor for poor prognosis of OC. Furthermore, Nck1 silencing by short hairpin RNA (shRNA) technology significantly inhibited the proliferation, migration and invasion of OC cells in vitro and the growth and metastasis of implanted OC tumors in vivo. Human kinase phosphorylation array indicated that Nck1 silencing significantly reduced the relative levels of 11 kinase expression and phosphorylation in OC cells, particularly for decreased levels of p70S6 kinase (p70S6K) and protein kinase B (AKT) expression in SKOV3 cells. Actually, Nck1 silencing significantly decreased PI3K and AKT expression, and reduced AKT and p70S6K phosphorylation while Nck1 over-expression had opposite effects in OC cells. Therefore, our data indicate that Nck1 promotes the progression of OC by enhancing the PI3k/AKT/p70S6K signaling in OC. Our findings suggest that Nck1 expression may be valuable for evaluating the prognosis of OC and as a target for design of new therapies for OC.</description><identifier>ISSN: 1749-0774</identifier><identifier>ISSN: 0914-7470</identifier><identifier>EISSN: 1749-0774</identifier><identifier>DOI: 10.1007/s13577-020-00344-8</identifier><identifier>PMID: 32166565</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adaptor Proteins, Signal Transducing - physiology ; AKT protein ; Biomedical and Life Sciences ; Carcinoma - genetics ; Carcinoma - therapy ; Cell Biology ; Cell Line, Tumor ; Cell proliferation ; Disease Progression ; Female ; Gynecology ; Humans ; Kinases ; Life Sciences ; Medical prognosis ; Metastases ; Molecular Targeted Therapy ; Oncogene Proteins - physiology ; Oncology ; Ovarian carcinoma ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - therapy ; Ovaries ; Overexpression ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Prognosis ; Protein-tyrosine kinase ; Proto-Oncogene Proteins c-akt - metabolism ; Reproductive Medicine ; Research Article ; Ribonucleic acid ; Ribosomal protein S6 kinase ; Ribosomal Protein S6 Kinases, 70-kDa - metabolism ; Risk factors ; RNA ; RNA-mediated interference ; Signal Transduction - genetics ; Signal Transduction - physiology ; Stem Cells ; Surgery ; Tumors</subject><ispartof>Human cell : official journal of Human Cell Research Society, 2020-07, Vol.33 (3), p.768-779</ispartof><rights>Japan Human Cell Society 2020</rights><rights>Japan Human Cell Society 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-65140f2bbbc6c8f1c43eae1507d3ac8ce19dc91f4f5a7cf0e4a2226932e56d043</citedby><cites>FETCH-LOGICAL-c375t-65140f2bbbc6c8f1c43eae1507d3ac8ce19dc91f4f5a7cf0e4a2226932e56d043</cites><orcidid>0000-0002-4882-6579</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13577-020-00344-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13577-020-00344-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32166565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Xiaohan</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Duan, Zhaoning</creatorcontrib><creatorcontrib>Feng, Xiushan</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Tang, Liangdan</creatorcontrib><title>Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling</title><title>Human cell : official journal of Human Cell Research Society</title><addtitle>Human Cell</addtitle><addtitle>Hum Cell</addtitle><description>Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ovarian tissues, and the up-regulated Nck1 expression is associated with the aggressiveness of OC and shorter overall and disease-free survival in this population. Higher Nck1 expression was an independent risk factor for poor prognosis of OC. Furthermore, Nck1 silencing by short hairpin RNA (shRNA) technology significantly inhibited the proliferation, migration and invasion of OC cells in vitro and the growth and metastasis of implanted OC tumors in vivo. Human kinase phosphorylation array indicated that Nck1 silencing significantly reduced the relative levels of 11 kinase expression and phosphorylation in OC cells, particularly for decreased levels of p70S6 kinase (p70S6K) and protein kinase B (AKT) expression in SKOV3 cells. Actually, Nck1 silencing significantly decreased PI3K and AKT expression, and reduced AKT and p70S6K phosphorylation while Nck1 over-expression had opposite effects in OC cells. Therefore, our data indicate that Nck1 promotes the progression of OC by enhancing the PI3k/AKT/p70S6K signaling in OC. Our findings suggest that Nck1 expression may be valuable for evaluating the prognosis of OC and as a target for design of new therapies for OC.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adaptor Proteins, Signal Transducing - physiology</subject><subject>AKT protein</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - therapy</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Molecular Targeted Therapy</subject><subject>Oncogene Proteins - physiology</subject><subject>Oncology</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Ovaries</subject><subject>Overexpression</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Prognosis</subject><subject>Protein-tyrosine kinase</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Reproductive Medicine</subject><subject>Research Article</subject><subject>Ribonucleic acid</subject><subject>Ribosomal protein S6 kinase</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</subject><subject>Risk factors</subject><subject>RNA</subject><subject>RNA-mediated interference</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Stem Cells</subject><subject>Surgery</subject><subject>Tumors</subject><issn>1749-0774</issn><issn>0914-7470</issn><issn>1749-0774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kElPwzAQhS0Eomx_gAOKxIVL6HhPjgixqQiQKEdkOY4TUpq42A1S_z1uyyYOnGZG8703o4fQIYZTDCCHAVMuZQoEUgDKWJptoB0sWZ6ClGzzVz9AuyFMABhngmyjASVYCC74Dnq-M684mXnXurkNyfzFLofa2xAa1yWuSty79o3uEqO9aTrX6qRYJLZ70V0c65Xi4YaOhmej8XAm4VGMktDUnZ7G7T7aqvQ02IPPuoeeLi_G59fp7f3VzfnZbWqo5PNUcMygIkVRGGGyChtGrbaYgyypNpmxOC9NjitWcS1NBZZpQojIKbFclMDoHjpZ-8bf33ob5qptgrHTqe6s64MiVErKRC4gosd_0InrfXw3UgxnkjPKlxRZU8a7ELyt1Mw3rfYLhUEtw1fr8FUMX63CV1kUHX1a90Vry2_JV9oRoGsgxFVXW_9z-x_bD-mVjeQ</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Liu, Xiaohan</creator><creator>Zhang, Jing</creator><creator>Duan, Zhaoning</creator><creator>Feng, Xiushan</creator><creator>Yu, Yang</creator><creator>He, Min</creator><creator>Tang, Liangdan</creator><general>Springer Singapore</general><general>Springer Nature B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0002-4882-6579</orcidid></search><sort><creationdate>20200701</creationdate><title>Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling</title><author>Liu, Xiaohan ; Zhang, Jing ; Duan, Zhaoning ; Feng, Xiushan ; Yu, Yang ; He, Min ; Tang, Liangdan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-65140f2bbbc6c8f1c43eae1507d3ac8ce19dc91f4f5a7cf0e4a2226932e56d043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adaptor Proteins, Signal Transducing - physiology</topic><topic>AKT protein</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - therapy</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Molecular Targeted Therapy</topic><topic>Oncogene Proteins - physiology</topic><topic>Oncology</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Ovaries</topic><topic>Overexpression</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Prognosis</topic><topic>Protein-tyrosine kinase</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Reproductive Medicine</topic><topic>Research Article</topic><topic>Ribonucleic acid</topic><topic>Ribosomal protein S6 kinase</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</topic><topic>Risk factors</topic><topic>RNA</topic><topic>RNA-mediated interference</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Stem Cells</topic><topic>Surgery</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Xiaohan</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Duan, Zhaoning</creatorcontrib><creatorcontrib>Feng, Xiushan</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Tang, Liangdan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human cell : official journal of Human Cell Research Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Xiaohan</au><au>Zhang, Jing</au><au>Duan, Zhaoning</au><au>Feng, Xiushan</au><au>Yu, Yang</au><au>He, Min</au><au>Tang, Liangdan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling</atitle><jtitle>Human cell : official journal of Human Cell Research Society</jtitle><stitle>Human Cell</stitle><addtitle>Hum Cell</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>33</volume><issue>3</issue><spage>768</spage><epage>779</epage><pages>768-779</pages><issn>1749-0774</issn><issn>0914-7470</issn><eissn>1749-0774</eissn><abstract>Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ovarian tissues, and the up-regulated Nck1 expression is associated with the aggressiveness of OC and shorter overall and disease-free survival in this population. Higher Nck1 expression was an independent risk factor for poor prognosis of OC. Furthermore, Nck1 silencing by short hairpin RNA (shRNA) technology significantly inhibited the proliferation, migration and invasion of OC cells in vitro and the growth and metastasis of implanted OC tumors in vivo. Human kinase phosphorylation array indicated that Nck1 silencing significantly reduced the relative levels of 11 kinase expression and phosphorylation in OC cells, particularly for decreased levels of p70S6 kinase (p70S6K) and protein kinase B (AKT) expression in SKOV3 cells. Actually, Nck1 silencing significantly decreased PI3K and AKT expression, and reduced AKT and p70S6K phosphorylation while Nck1 over-expression had opposite effects in OC cells. Therefore, our data indicate that Nck1 promotes the progression of OC by enhancing the PI3k/AKT/p70S6K signaling in OC. Our findings suggest that Nck1 expression may be valuable for evaluating the prognosis of OC and as a target for design of new therapies for OC.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>32166565</pmid><doi>10.1007/s13577-020-00344-8</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4882-6579</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1749-0774
ispartof Human cell : official journal of Human Cell Research Society, 2020-07, Vol.33 (3), p.768-779
issn 1749-0774
0914-7470
1749-0774
language eng
recordid cdi_proquest_miscellaneous_2377346960
source MEDLINE; SpringerLink Journals
subjects 1-Phosphatidylinositol 3-kinase
Adaptor Proteins, Signal Transducing - physiology
AKT protein
Biomedical and Life Sciences
Carcinoma - genetics
Carcinoma - therapy
Cell Biology
Cell Line, Tumor
Cell proliferation
Disease Progression
Female
Gynecology
Humans
Kinases
Life Sciences
Medical prognosis
Metastases
Molecular Targeted Therapy
Oncogene Proteins - physiology
Oncology
Ovarian carcinoma
Ovarian Neoplasms - genetics
Ovarian Neoplasms - therapy
Ovaries
Overexpression
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Prognosis
Protein-tyrosine kinase
Proto-Oncogene Proteins c-akt - metabolism
Reproductive Medicine
Research Article
Ribonucleic acid
Ribosomal protein S6 kinase
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Risk factors
RNA
RNA-mediated interference
Signal Transduction - genetics
Signal Transduction - physiology
Stem Cells
Surgery
Tumors
title Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T20%3A20%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nck1%20promotes%20the%20progression%20of%20ovarian%20carcinoma%20by%20enhancing%20the%20PI3K/AKT/p70S6K%20signaling&rft.jtitle=Human%20cell%20:%20official%20journal%20of%20Human%20Cell%20Research%20Society&rft.au=Liu,%20Xiaohan&rft.date=2020-07-01&rft.volume=33&rft.issue=3&rft.spage=768&rft.epage=779&rft.pages=768-779&rft.issn=1749-0774&rft.eissn=1749-0774&rft_id=info:doi/10.1007/s13577-020-00344-8&rft_dat=%3Cproquest_cross%3E2377346960%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2418754350&rft_id=info:pmid/32166565&rfr_iscdi=true