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...
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Veröffentlicht in: | Human cell : official journal of Human Cell Research Society 2020-07, Vol.33 (3), p.768-779 |
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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. |
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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> |
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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 |
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