Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2013-12, Vol.8 (12), p.e84457
Hauptverfasser: Tian, Yuan, Ding, Wencheng, Wang, Yingying, Ji, Teng, Sun, Shujuan, Mo, Qingqing, Chen, Pingbo, Fang, Yong, Liu, Jia, Wang, Beibei, Zhou, Jianfeng, Ma, Ding, Wu, Peng
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 12
container_start_page e84457
container_title PloS one
container_volume 8
creator Tian, Yuan
Ding, Wencheng
Wang, Yingying
Ji, Teng
Sun, Shujuan
Mo, Qingqing
Chen, Pingbo
Fang, Yong
Liu, Jia
Wang, Beibei
Zhou, Jianfeng
Ma, Ding
Wu, Peng
description Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.
doi_str_mv 10.1371/journal.pone.0084457
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1469304928</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478229705</galeid><doaj_id>oai_doaj_org_article_d3581d9739e44e9caf17df9d3b784b27</doaj_id><sourcerecordid>A478229705</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-65cdc1d0b928b728ccb7c0af40ef169d85430833416898832484263a62190b8b3</originalsourceid><addsrcrecordid>eNqNkmuL1DAUhoso7kX_gWhBWPBDx9yaix-EdfEysLCgrl9jmqbTjG0zm6SL_ntTp7tMQUEKaTjned-kp2-WPYNgBTGDr7du9IPqVjs3mBUAnJCSPciOocCooAjghwf7o-wkhC0AJeaUPs6OEMGUUQqPs-_Xlb0ZbbRD_i5Pizb-1mrV5VoNaf8m1z41p0LjfB5bk_fKDtEMUzt3zczlIZq-6OwPkxy6pG6VVzoaH55kjxrVBfN0fp9m1x_ef734VFxefVxfnF8WmpU8FrTUtYY1qATiFUNc64ppoBoCTAOpqHlJMOAYE0i54BwjwgmiWFEEBah4hU-zF3vfXeeCnIcTJCRUYECSayLWe6J2ait33vbK_5JOWfmn4PxGKp--tTOyxiWHtWBYGEKM0KqBrG5EjSvGSYVY8no7nzZWvam1GaJX3cJ02RlsKzfuVqYfwAgvk8HL2cC7m9GE-I8rz9RGpVvZoXHJTPc2aHlOGEdIMDB5rf5Cpac2vdUpHo1N9YXg1UKQmGh-xo0aQ5DrL5__n736tmTPDtjWqC62wXVjtG4IS5DsQe1dCN4095ODQE7pvpuGnNIt53Qn2fPDqd-L7uKMfwOtjfO_</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1469304928</pqid></control><display><type>article</type><title>Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Tian, Yuan ; Ding, Wencheng ; Wang, Yingying ; Ji, Teng ; Sun, Shujuan ; Mo, Qingqing ; Chen, Pingbo ; Fang, Yong ; Liu, Jia ; Wang, Beibei ; Zhou, Jianfeng ; Ma, Ding ; Wu, Peng</creator><contributor>Ahmad, Aamir</contributor><creatorcontrib>Tian, Yuan ; Ding, Wencheng ; Wang, Yingying ; Ji, Teng ; Sun, Shujuan ; Mo, Qingqing ; Chen, Pingbo ; Fang, Yong ; Liu, Jia ; Wang, Beibei ; Zhou, Jianfeng ; Ma, Ding ; Wu, Peng ; Ahmad, Aamir</creatorcontrib><description>Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0084457</identifier><identifier>PMID: 24367661</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Biodegradation ; Biology ; Biomarkers ; Breast cancer ; Cancer ; Cancer therapies ; Cell cycle ; Cell proliferation ; Cell Transformation, Neoplastic - drug effects ; Cervical cancer ; Cervix ; Chemoresistance ; Chemotherapy ; Cosmetics industry ; Degradation ; Disease ; Drug resistance ; Drug Resistance, Neoplasm - drug effects ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Silencing ; Genes ; HeLa Cells ; Histone deacetylase ; Histone Deacetylase Inhibitors - pharmacology ; Hospitals ; Humans ; Hydroxamic Acids - pharmacology ; Hypotheses ; Malignancy ; Mice ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Oct-4 protein ; Pathology ; Proteasomes ; Proteins ; Proteolysis ; RNA, Small Interfering - genetics ; Science ; Selectivity ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - pathology ; Squamous cell carcinoma ; Stem cells ; Trichostatin A ; Tumors ; Turnover rate ; Ubiquitin ; Ubiquitin - deficiency ; Ubiquitin - genetics ; Ubiquitin - metabolism ; Up-Regulation - drug effects ; Uterine Cervical Neoplasms - drug therapy ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - pathology ; Vaccines ; Western blotting ; Xenografts</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e84457</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Tian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Tian et al 2013 Tian et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-65cdc1d0b928b728ccb7c0af40ef169d85430833416898832484263a62190b8b3</citedby><cites>FETCH-LOGICAL-c758t-65cdc1d0b928b728ccb7c0af40ef169d85430833416898832484263a62190b8b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867485/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867485/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24367661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ahmad, Aamir</contributor><creatorcontrib>Tian, Yuan</creatorcontrib><creatorcontrib>Ding, Wencheng</creatorcontrib><creatorcontrib>Wang, Yingying</creatorcontrib><creatorcontrib>Ji, Teng</creatorcontrib><creatorcontrib>Sun, Shujuan</creatorcontrib><creatorcontrib>Mo, Qingqing</creatorcontrib><creatorcontrib>Chen, Pingbo</creatorcontrib><creatorcontrib>Fang, Yong</creatorcontrib><creatorcontrib>Liu, Jia</creatorcontrib><creatorcontrib>Wang, Beibei</creatorcontrib><creatorcontrib>Zhou, Jianfeng</creatorcontrib><creatorcontrib>Ma, Ding</creatorcontrib><creatorcontrib>Wu, Peng</creatorcontrib><title>Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biodegradation</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Cell Transformation, Neoplastic - drug effects</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Cosmetics industry</subject><subject>Degradation</subject><subject>Disease</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Silencing</subject><subject>Genes</subject><subject>HeLa Cells</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Hypotheses</subject><subject>Malignancy</subject><subject>Mice</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Oct-4 protein</subject><subject>Pathology</subject><subject>Proteasomes</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>RNA, Small Interfering - genetics</subject><subject>Science</subject><subject>Selectivity</subject><subject>Spheroids, Cellular - drug effects</subject><subject>Spheroids, Cellular - pathology</subject><subject>Squamous cell carcinoma</subject><subject>Stem cells</subject><subject>Trichostatin A</subject><subject>Tumors</subject><subject>Turnover rate</subject><subject>Ubiquitin</subject><subject>Ubiquitin - deficiency</subject><subject>Ubiquitin - genetics</subject><subject>Ubiquitin - metabolism</subject><subject>Up-Regulation - drug effects</subject><subject>Uterine Cervical Neoplasms - drug therapy</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Vaccines</subject><subject>Western blotting</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkmuL1DAUhoso7kX_gWhBWPBDx9yaix-EdfEysLCgrl9jmqbTjG0zm6SL_ntTp7tMQUEKaTjned-kp2-WPYNgBTGDr7du9IPqVjs3mBUAnJCSPciOocCooAjghwf7o-wkhC0AJeaUPs6OEMGUUQqPs-_Xlb0ZbbRD_i5Pizb-1mrV5VoNaf8m1z41p0LjfB5bk_fKDtEMUzt3zczlIZq-6OwPkxy6pG6VVzoaH55kjxrVBfN0fp9m1x_ef734VFxefVxfnF8WmpU8FrTUtYY1qATiFUNc64ppoBoCTAOpqHlJMOAYE0i54BwjwgmiWFEEBah4hU-zF3vfXeeCnIcTJCRUYECSayLWe6J2ait33vbK_5JOWfmn4PxGKp--tTOyxiWHtWBYGEKM0KqBrG5EjSvGSYVY8no7nzZWvam1GaJX3cJ02RlsKzfuVqYfwAgvk8HL2cC7m9GE-I8rz9RGpVvZoXHJTPc2aHlOGEdIMDB5rf5Cpac2vdUpHo1N9YXg1UKQmGh-xo0aQ5DrL5__n736tmTPDtjWqC62wXVjtG4IS5DsQe1dCN4095ODQE7pvpuGnNIt53Qn2fPDqd-L7uKMfwOtjfO_</recordid><startdate>20131218</startdate><enddate>20131218</enddate><creator>Tian, Yuan</creator><creator>Ding, Wencheng</creator><creator>Wang, Yingying</creator><creator>Ji, Teng</creator><creator>Sun, Shujuan</creator><creator>Mo, Qingqing</creator><creator>Chen, Pingbo</creator><creator>Fang, Yong</creator><creator>Liu, Jia</creator><creator>Wang, Beibei</creator><creator>Zhou, Jianfeng</creator><creator>Ma, Ding</creator><creator>Wu, Peng</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131218</creationdate><title>Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters</title><author>Tian, Yuan ; Ding, Wencheng ; Wang, Yingying ; Ji, Teng ; Sun, Shujuan ; Mo, Qingqing ; Chen, Pingbo ; Fang, Yong ; Liu, Jia ; Wang, Beibei ; Zhou, Jianfeng ; Ma, Ding ; Wu, Peng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-65cdc1d0b928b728ccb7c0af40ef169d85430833416898832484263a62190b8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biodegradation</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell proliferation</topic><topic>Cell Transformation, Neoplastic - drug effects</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Cosmetics industry</topic><topic>Degradation</topic><topic>Disease</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Silencing</topic><topic>Genes</topic><topic>HeLa Cells</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Hypotheses</topic><topic>Malignancy</topic><topic>Mice</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Oct-4 protein</topic><topic>Pathology</topic><topic>Proteasomes</topic><topic>Proteins</topic><topic>Proteolysis</topic><topic>RNA, Small Interfering - genetics</topic><topic>Science</topic><topic>Selectivity</topic><topic>Spheroids, Cellular - drug effects</topic><topic>Spheroids, Cellular - pathology</topic><topic>Squamous cell carcinoma</topic><topic>Stem cells</topic><topic>Trichostatin A</topic><topic>Tumors</topic><topic>Turnover rate</topic><topic>Ubiquitin</topic><topic>Ubiquitin - deficiency</topic><topic>Ubiquitin - genetics</topic><topic>Ubiquitin - metabolism</topic><topic>Up-Regulation - drug effects</topic><topic>Uterine Cervical Neoplasms - drug therapy</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Vaccines</topic><topic>Western blotting</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Yuan</creatorcontrib><creatorcontrib>Ding, Wencheng</creatorcontrib><creatorcontrib>Wang, Yingying</creatorcontrib><creatorcontrib>Ji, Teng</creatorcontrib><creatorcontrib>Sun, Shujuan</creatorcontrib><creatorcontrib>Mo, Qingqing</creatorcontrib><creatorcontrib>Chen, Pingbo</creatorcontrib><creatorcontrib>Fang, Yong</creatorcontrib><creatorcontrib>Liu, Jia</creatorcontrib><creatorcontrib>Wang, Beibei</creatorcontrib><creatorcontrib>Zhou, Jianfeng</creatorcontrib><creatorcontrib>Ma, Ding</creatorcontrib><creatorcontrib>Wu, Peng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tian, Yuan</au><au>Ding, Wencheng</au><au>Wang, Yingying</au><au>Ji, Teng</au><au>Sun, Shujuan</au><au>Mo, Qingqing</au><au>Chen, Pingbo</au><au>Fang, Yong</au><au>Liu, Jia</au><au>Wang, Beibei</au><au>Zhou, Jianfeng</au><au>Ma, Ding</au><au>Wu, Peng</au><au>Ahmad, Aamir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-18</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e84457</spage><pages>e84457-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24367661</pmid><doi>10.1371/journal.pone.0084457</doi><tpages>e84457</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2013-12, Vol.8 (12), p.e84457
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1469304928
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry
subjects Animals
Apoptosis
Biodegradation
Biology
Biomarkers
Breast cancer
Cancer
Cancer therapies
Cell cycle
Cell proliferation
Cell Transformation, Neoplastic - drug effects
Cervical cancer
Cervix
Chemoresistance
Chemotherapy
Cosmetics industry
Degradation
Disease
Drug resistance
Drug Resistance, Neoplasm - drug effects
Female
Gene Expression Regulation, Neoplastic - drug effects
Gene Silencing
Genes
HeLa Cells
Histone deacetylase
Histone Deacetylase Inhibitors - pharmacology
Hospitals
Humans
Hydroxamic Acids - pharmacology
Hypotheses
Malignancy
Mice
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Oct-4 protein
Pathology
Proteasomes
Proteins
Proteolysis
RNA, Small Interfering - genetics
Science
Selectivity
Spheroids, Cellular - drug effects
Spheroids, Cellular - pathology
Squamous cell carcinoma
Stem cells
Trichostatin A
Tumors
Turnover rate
Ubiquitin
Ubiquitin - deficiency
Ubiquitin - genetics
Ubiquitin - metabolism
Up-Regulation - drug effects
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
Vaccines
Western blotting
Xenografts
title Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T23%3A35%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ubiquitin%20B%20in%20cervical%20cancer:%20critical%20for%20the%20maintenance%20of%20cancer%20stem-like%20cell%20characters&rft.jtitle=PloS%20one&rft.au=Tian,%20Yuan&rft.date=2013-12-18&rft.volume=8&rft.issue=12&rft.spage=e84457&rft.pages=e84457-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0084457&rft_dat=%3Cgale_plos_%3EA478229705%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1469304928&rft_id=info:pmid/24367661&rft_galeid=A478229705&rft_doaj_id=oai_doaj_org_article_d3581d9739e44e9caf17df9d3b784b27&rfr_iscdi=true