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Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells
Epithelial–mesenchymal transition (EMT) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcri...
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| Published in: | Cancer medicine (Malden, MA) MA), 2012-08, Vol.1 (1), p.5-16 |
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| creator | Fan, Fan Samuel, Shaija Evans, Kurt W. Lu, Jia Xia, Ling Zhou, Yunfei Sceusi, Eric Tozzi, Federico Ye, Xiang‐Cang Mani, Sendurai A. Ellis, Lee M. |
| description | Epithelial–mesenchymal transition (EMT) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcription factor that mediates EMT in a number of tumor types, including colorectal cancer (CRC). Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC. Human CRC specimens were stained for Snail expression, and human CRC cell lines were transduced with a retroviral Snail construct or vector control. Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT (colorimetric 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Migration and invasion were determined in vitro using modified Boyden chamber assays. EMT and putative CSC markers were analyzed using Western blotting. Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice. Snail was overexpressed in human CRC surgical specimens. This overexpression induced EMT and a CSC‐like phenotype in human CRC cells and enhanced cell migration and invasion (P |
| doi_str_mv | 10.1002/cam4.4 |
| format | article |
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Novelty and impact of the paper
We found that Snail, a transcription factor that mediates epithelial‐to‐mesenchymal transition (EMT), was overexpressed in human colorectal cancer (CRC) specimens. Snail overexpression in human CRC cells by retroviral infection led to an increase in the EMT and the cancer stem cell‐like phenotype. In addition, Snail‐mediated chemoresistance in CRC cells in vitro and metastasis in vivo. Snail is a potential therapeutic target in CRC and inhibition of Snail activity may serve as a novel method to enhance the efficacy of chemotherapy and improve outcomes of patients with metastatic CRC.</description><identifier>ISSN: 2045-7634</identifier><identifier>EISSN: 2045-7634</identifier><identifier>DOI: 10.1002/cam4.4</identifier><identifier>PMID: 23342249</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Animals ; Boyden chamber ; Breast cancer ; Cancer Biology ; Cancer stem cells ; Cancer therapies ; Cell Line ; Cell migration ; Cell Movement - genetics ; Cell proliferation ; Chemoresistance ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Colorimetry ; Cytokines ; Drug Resistance, Neoplasm - genetics ; EMT ; Epithelial-Mesenchymal Transition ; Flow cytometry ; Gene Expression ; Genotype & phenotype ; Heterografts ; Humans ; Immunoglobulins ; Intravenous administration ; Kinases ; Mesenchyme ; Metastases ; Metastasis ; Mice ; migration ; Motility ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplastic Stem Cells - metabolism ; Ovarian cancer ; Oxaliplatin ; Phenotype ; Phenotypes ; Proteins ; Snail ; Snail Family Transcription Factors ; Snail protein ; Stem cells ; Therapeutic applications ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumor cells ; Tumors ; Western blotting</subject><ispartof>Cancer medicine (Malden, MA), 2012-08, Vol.1 (1), p.5-16</ispartof><rights>2012 The Authors. published by Blackwell Publishing Ltd.</rights><rights>2012. This work is published under http://creativecommons.org/licenses/by-nc/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>2012 The Authors. Published by Blackwell Publishing Ltd. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4944-9d63c66d615f1bc00abcff47cbbc237cedca8476eae47336e9e2f45bfb7339163</citedby><cites>FETCH-LOGICAL-c4944-9d63c66d615f1bc00abcff47cbbc237cedca8476eae47336e9e2f45bfb7339163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2290417036/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2290417036?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11562,25753,27924,27925,37012,37013,44590,46052,46476,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23342249$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Fan</creatorcontrib><creatorcontrib>Samuel, Shaija</creatorcontrib><creatorcontrib>Evans, Kurt W.</creatorcontrib><creatorcontrib>Lu, Jia</creatorcontrib><creatorcontrib>Xia, Ling</creatorcontrib><creatorcontrib>Zhou, Yunfei</creatorcontrib><creatorcontrib>Sceusi, Eric</creatorcontrib><creatorcontrib>Tozzi, Federico</creatorcontrib><creatorcontrib>Ye, Xiang‐Cang</creatorcontrib><creatorcontrib>Mani, Sendurai A.</creatorcontrib><creatorcontrib>Ellis, Lee M.</creatorcontrib><title>Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells</title><title>Cancer medicine (Malden, MA)</title><addtitle>Cancer Med</addtitle><description>Epithelial–mesenchymal transition (EMT) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcription factor that mediates EMT in a number of tumor types, including colorectal cancer (CRC). Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC. Human CRC specimens were stained for Snail expression, and human CRC cell lines were transduced with a retroviral Snail construct or vector control. Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT (colorimetric 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Migration and invasion were determined in vitro using modified Boyden chamber assays. EMT and putative CSC markers were analyzed using Western blotting. Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice. Snail was overexpressed in human CRC surgical specimens. This overexpression induced EMT and a CSC‐like phenotype in human CRC cells and enhanced cell migration and invasion (P < 0.002 vs. control). Snail overexpression also led to an increase in metastasis formation in vivo (P < 0.002 vs. control). Furthermore, the Snail‐overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells. Increased Snail expression induces EMT and the CSC‐like phenotype in CRC cells, which enhance cancer cell invasion and chemoresistance. Thus, Snail is a potential therapeutic target in metastatic CRC.
Novelty and impact of the paper
We found that Snail, a transcription factor that mediates epithelial‐to‐mesenchymal transition (EMT), was overexpressed in human colorectal cancer (CRC) specimens. Snail overexpression in human CRC cells by retroviral infection led to an increase in the EMT and the cancer stem cell‐like phenotype. In addition, Snail‐mediated chemoresistance in CRC cells in vitro and metastasis in vivo. Snail is a potential therapeutic target in CRC and inhibition of Snail activity may serve as a novel method to enhance the efficacy of chemotherapy and improve outcomes of patients with metastatic CRC.</description><subject>Animals</subject><subject>Boyden chamber</subject><subject>Breast cancer</subject><subject>Cancer Biology</subject><subject>Cancer stem cells</subject><subject>Cancer therapies</subject><subject>Cell Line</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cell proliferation</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorimetry</subject><subject>Cytokines</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>EMT</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Flow cytometry</subject><subject>Gene Expression</subject><subject>Genotype & phenotype</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Intravenous administration</subject><subject>Kinases</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>migration</subject><subject>Motility</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Ovarian cancer</subject><subject>Oxaliplatin</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Proteins</subject><subject>Snail</subject><subject>Snail Family Transcription Factors</subject><subject>Snail protein</subject><subject>Stem cells</subject><subject>Therapeutic applications</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Western blotting</subject><issn>2045-7634</issn><issn>2045-7634</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><recordid>eNp1kc9qFTEYxYNYbGnrI0hAkLq4Nf8mcTZCuWgttHShrkMm842TmknGZKZ6dz6AO9-wT2KGey1VMJsk5HdOvsNB6Cklp5QQ9sqaQZyKR-iAEVGtlOTi8YPzPjrO-YaUpQiTij5B-4xzwZioD9DP61tI8H1MkLOLAccOfwjGeexCO1vIGEY39eCd8Xc_fg2QIdh-MxiPp2RCdtMiMqHFBlsTLCScJxiwBb_w3n0BPPYQ4rQZoXjifh5MwDb6mMBOxWanWgT5CO11xmc43u2H6NO7tx_X71eX1-cX67PLlRW1EKu6ldxK2UpadbSxhJjGdp1Qtmks48pCa81roSQYEIpzCTWwTlRN15RbTSU_RG-2vuPcDIWGUMJ4PSY3mLTR0Tj990twvf4cbzWvhBCcFIOTnUGKX2fIkx5cXiKYAHHOmjLFVa1otfz1_B_0Js4plHiasZoIqghfqBdbyqaYc4LufhhK9NKxXjrWooDPHo5-j_1ptAAvt8A352HzHxu9PrsqQX4DlA-06g</recordid><startdate>201208</startdate><enddate>201208</enddate><creator>Fan, Fan</creator><creator>Samuel, Shaija</creator><creator>Evans, Kurt W.</creator><creator>Lu, Jia</creator><creator>Xia, Ling</creator><creator>Zhou, Yunfei</creator><creator>Sceusi, Eric</creator><creator>Tozzi, Federico</creator><creator>Ye, Xiang‐Cang</creator><creator>Mani, Sendurai A.</creator><creator>Ellis, Lee M.</creator><general>John Wiley & Sons, Inc</general><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>WIN</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</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></search><sort><creationdate>201208</creationdate><title>Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells</title><author>Fan, Fan ; Samuel, Shaija ; Evans, Kurt W. ; Lu, Jia ; Xia, Ling ; Zhou, Yunfei ; Sceusi, Eric ; Tozzi, Federico ; Ye, Xiang‐Cang ; Mani, Sendurai A. ; Ellis, Lee M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4944-9d63c66d615f1bc00abcff47cbbc237cedca8476eae47336e9e2f45bfb7339163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Boyden chamber</topic><topic>Breast cancer</topic><topic>Cancer Biology</topic><topic>Cancer stem cells</topic><topic>Cancer therapies</topic><topic>Cell Line</topic><topic>Cell migration</topic><topic>Cell Movement - genetics</topic><topic>Cell proliferation</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Colorimetry</topic><topic>Cytokines</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>EMT</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Flow cytometry</topic><topic>Gene Expression</topic><topic>Genotype & phenotype</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Intravenous administration</topic><topic>Kinases</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>migration</topic><topic>Motility</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Ovarian cancer</topic><topic>Oxaliplatin</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Proteins</topic><topic>Snail</topic><topic>Snail Family Transcription Factors</topic><topic>Snail protein</topic><topic>Stem cells</topic><topic>Therapeutic applications</topic><topic>Transcription factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Fan</creatorcontrib><creatorcontrib>Samuel, Shaija</creatorcontrib><creatorcontrib>Evans, Kurt W.</creatorcontrib><creatorcontrib>Lu, Jia</creatorcontrib><creatorcontrib>Xia, Ling</creatorcontrib><creatorcontrib>Zhou, Yunfei</creatorcontrib><creatorcontrib>Sceusi, Eric</creatorcontrib><creatorcontrib>Tozzi, Federico</creatorcontrib><creatorcontrib>Ye, Xiang‐Cang</creatorcontrib><creatorcontrib>Mani, Sendurai A.</creatorcontrib><creatorcontrib>Ellis, Lee M.</creatorcontrib><collection>Open Access: Wiley-Blackwell Open Access Journals</collection><collection>Wiley Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest - 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>Cancer medicine (Malden, MA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Fan</au><au>Samuel, Shaija</au><au>Evans, Kurt W.</au><au>Lu, Jia</au><au>Xia, Ling</au><au>Zhou, Yunfei</au><au>Sceusi, Eric</au><au>Tozzi, Federico</au><au>Ye, Xiang‐Cang</au><au>Mani, Sendurai A.</au><au>Ellis, Lee M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells</atitle><jtitle>Cancer medicine (Malden, MA)</jtitle><addtitle>Cancer Med</addtitle><date>2012-08</date><risdate>2012</risdate><volume>1</volume><issue>1</issue><spage>5</spage><epage>16</epage><pages>5-16</pages><issn>2045-7634</issn><eissn>2045-7634</eissn><abstract>Epithelial–mesenchymal transition (EMT) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcription factor that mediates EMT in a number of tumor types, including colorectal cancer (CRC). Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC. Human CRC specimens were stained for Snail expression, and human CRC cell lines were transduced with a retroviral Snail construct or vector control. Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT (colorimetric 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Migration and invasion were determined in vitro using modified Boyden chamber assays. EMT and putative CSC markers were analyzed using Western blotting. Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice. Snail was overexpressed in human CRC surgical specimens. This overexpression induced EMT and a CSC‐like phenotype in human CRC cells and enhanced cell migration and invasion (P < 0.002 vs. control). Snail overexpression also led to an increase in metastasis formation in vivo (P < 0.002 vs. control). Furthermore, the Snail‐overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells. Increased Snail expression induces EMT and the CSC‐like phenotype in CRC cells, which enhance cancer cell invasion and chemoresistance. Thus, Snail is a potential therapeutic target in metastatic CRC.
Novelty and impact of the paper
We found that Snail, a transcription factor that mediates epithelial‐to‐mesenchymal transition (EMT), was overexpressed in human colorectal cancer (CRC) specimens. Snail overexpression in human CRC cells by retroviral infection led to an increase in the EMT and the cancer stem cell‐like phenotype. In addition, Snail‐mediated chemoresistance in CRC cells in vitro and metastasis in vivo. Snail is a potential therapeutic target in CRC and inhibition of Snail activity may serve as a novel method to enhance the efficacy of chemotherapy and improve outcomes of patients with metastatic CRC.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>23342249</pmid><doi>10.1002/cam4.4</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer medicine (Malden, MA), 2012-08, Vol.1 (1), p.5-16 |
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| source | Open Access: Wiley-Blackwell Open Access Journals; PubMed Central Free; ProQuest - Publicly Available Content Database |
| subjects | Animals Boyden chamber Breast cancer Cancer Biology Cancer stem cells Cancer therapies Cell Line Cell migration Cell Movement - genetics Cell proliferation Chemoresistance Chemotherapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Colorimetry Cytokines Drug Resistance, Neoplasm - genetics EMT Epithelial-Mesenchymal Transition Flow cytometry Gene Expression Genotype & phenotype Heterografts Humans Immunoglobulins Intravenous administration Kinases Mesenchyme Metastases Metastasis Mice migration Motility Neoplasm Invasiveness Neoplasm Metastasis Neoplastic Stem Cells - metabolism Ovarian cancer Oxaliplatin Phenotype Phenotypes Proteins Snail Snail Family Transcription Factors Snail protein Stem cells Therapeutic applications Transcription factors Transcription Factors - genetics Transcription Factors - metabolism Tumor cells Tumors Western blotting |
| title | Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells |
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