Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer
Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this st...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-02, Vol.8 (2), p.e56664-e56664 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e56664 |
|---|---|
| container_issue | 2 |
| container_start_page | e56664 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Wang, Hao Wang, Hong-Sheng Zhou, Bin-Hua Li, Cui-Lin Zhang, Fan Wang, Xian-Feng Zhang, Ge Bu, Xian-Zhang Cai, Shao-Hui Du, Jun |
| description | Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis. |
| doi_str_mv | 10.1371/journal.pone.0056664 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1330882282</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_f57e1735af504ec3ae6e6a5441cf0d84</doaj_id><sourcerecordid>2949773261</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-8a18ed0d1b2b551671a04dd78a901b54ae340dcb82f04db084d3849a232635a3</originalsourceid><addsrcrecordid>eNptks1uEzEQx1cIREvhDRCsxKUcNvXXercXpKpKS9UCB3K3Zu3ZxpFjp_YuUrjyRPAgfSacJq1axMmj8X9-86F_UbylZEJ5Q48WYYwe3GQVPE4IqaWU4lmxT485qyQj_PmjeK94ldIii3gr5ctij3HBaY73i1_TlR3m6Cy4aokJvZ6vl-DKIYJPdrDBl4fTL7OPpfVm1GjKbl3Ovp5Vt7_LiDejjZjKk8vZ0fn3y4rf_skMY2HIujRAZ539CXeM0JfJg3UZU-rgQkQ95C4avMb4unjRg0v4ZvceFLOz6ez0c3X17fzi9OSq0jWTQ9UCbdEQQzvW1TWVDQUijGlaOCa0qwUgF8TormV9znekFYa34hgYZ5LXwA-K91vsyoWkdudLinJO2paxlmXFxVZhAizUKtolxLUKYNVdIsRrBXGw2qHq6wZpk7F9TQRqDihRQi0E1T0xrcisT7tuY5ePotHnk7on0Kc_3s7VdfiheN1ILpoMONwBYrgZMQ1qaZNG58BjGDdzU0Yblq2QpR_-kf5_O7FV6RhSitg_DEOJ2ljqvkptLKV2lspl7x4v8lB07yH-F5c2y7g</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1330882282</pqid></control><display><type>article</type><title>Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Wang, Hao ; Wang, Hong-Sheng ; Zhou, Bin-Hua ; Li, Cui-Lin ; Zhang, Fan ; Wang, Xian-Feng ; Zhang, Ge ; Bu, Xian-Zhang ; Cai, Shao-Hui ; Du, Jun</creator><creatorcontrib>Wang, Hao ; Wang, Hong-Sheng ; Zhou, Bin-Hua ; Li, Cui-Lin ; Zhang, Fan ; Wang, Xian-Feng ; Zhang, Ge ; Bu, Xian-Zhang ; Cai, Shao-Hui ; Du, Jun</creatorcontrib><description>Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0056664</identifier><identifier>PMID: 23431386</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Biology ; Breast cancer ; Caco-2 Cells ; Cancer ; Cell adhesion & migration ; Cell Movement ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms ; Cytokines ; E-cadherin ; Epithelial-Mesenchymal Transition ; Fibronectin ; Gene expression ; Gene Knockdown Techniques ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; HCT116 Cells ; Humans ; Inflammation ; Kinases ; Localization ; Lymphatic system ; Medical research ; Medicine ; Mesenchyme ; Metastases ; Metastasis ; Motility ; N-Cadherin ; Pharmaceutical sciences ; Pharmacy ; Protein Binding ; Protein Stability ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Small Interfering - genetics ; Signal Transduction ; Snail Family Transcription Factors ; Snail protein ; Stabilization ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumor Necrosis Factor-alpha - physiology ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Ubiquitination ; Zonula occludens-1 protein</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e56664-e56664</ispartof><rights>2013 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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 Wang et al 2013 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-8a18ed0d1b2b551671a04dd78a901b54ae340dcb82f04db084d3849a232635a3</citedby><cites>FETCH-LOGICAL-c526t-8a18ed0d1b2b551671a04dd78a901b54ae340dcb82f04db084d3849a232635a3</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/PMC3576347/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576347/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23431386$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Hao</creatorcontrib><creatorcontrib>Wang, Hong-Sheng</creatorcontrib><creatorcontrib>Zhou, Bin-Hua</creatorcontrib><creatorcontrib>Li, Cui-Lin</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Wang, Xian-Feng</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>Bu, Xian-Zhang</creatorcontrib><creatorcontrib>Cai, Shao-Hui</creatorcontrib><creatorcontrib>Du, Jun</creatorcontrib><title>Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis.</description><subject>AKT protein</subject><subject>Biology</subject><subject>Breast cancer</subject><subject>Caco-2 Cells</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell Movement</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms</subject><subject>Cytokines</subject><subject>E-cadherin</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Fibronectin</subject><subject>Gene expression</subject><subject>Gene Knockdown Techniques</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Localization</subject><subject>Lymphatic system</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Motility</subject><subject>N-Cadherin</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacy</subject><subject>Protein Binding</subject><subject>Protein Stability</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal Transduction</subject><subject>Snail Family Transcription Factors</subject><subject>Snail protein</subject><subject>Stabilization</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Ubiquitination</subject><subject>Zonula occludens-1 protein</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptks1uEzEQx1cIREvhDRCsxKUcNvXXercXpKpKS9UCB3K3Zu3ZxpFjp_YuUrjyRPAgfSacJq1axMmj8X9-86F_UbylZEJ5Q48WYYwe3GQVPE4IqaWU4lmxT485qyQj_PmjeK94ldIii3gr5ctij3HBaY73i1_TlR3m6Cy4aokJvZ6vl-DKIYJPdrDBl4fTL7OPpfVm1GjKbl3Ovp5Vt7_LiDejjZjKk8vZ0fn3y4rf_skMY2HIujRAZ539CXeM0JfJg3UZU-rgQkQ95C4avMb4unjRg0v4ZvceFLOz6ez0c3X17fzi9OSq0jWTQ9UCbdEQQzvW1TWVDQUijGlaOCa0qwUgF8TormV9znekFYa34hgYZ5LXwA-K91vsyoWkdudLinJO2paxlmXFxVZhAizUKtolxLUKYNVdIsRrBXGw2qHq6wZpk7F9TQRqDihRQi0E1T0xrcisT7tuY5ePotHnk7on0Kc_3s7VdfiheN1ILpoMONwBYrgZMQ1qaZNG58BjGDdzU0Yblq2QpR_-kf5_O7FV6RhSitg_DEOJ2ljqvkptLKV2lspl7x4v8lB07yH-F5c2y7g</recordid><startdate>20130219</startdate><enddate>20130219</enddate><creator>Wang, Hao</creator><creator>Wang, Hong-Sheng</creator><creator>Zhou, Bin-Hua</creator><creator>Li, Cui-Lin</creator><creator>Zhang, Fan</creator><creator>Wang, Xian-Feng</creator><creator>Zhang, Ge</creator><creator>Bu, Xian-Zhang</creator><creator>Cai, Shao-Hui</creator><creator>Du, Jun</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>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>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130219</creationdate><title>Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer</title><author>Wang, Hao ; Wang, Hong-Sheng ; Zhou, Bin-Hua ; Li, Cui-Lin ; Zhang, Fan ; Wang, Xian-Feng ; Zhang, Ge ; Bu, Xian-Zhang ; Cai, Shao-Hui ; Du, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-8a18ed0d1b2b551671a04dd78a901b54ae340dcb82f04db084d3849a232635a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>AKT protein</topic><topic>Biology</topic><topic>Breast cancer</topic><topic>Caco-2 Cells</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell Movement</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms</topic><topic>Cytokines</topic><topic>E-cadherin</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Fibronectin</topic><topic>Gene expression</topic><topic>Gene Knockdown Techniques</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Localization</topic><topic>Lymphatic system</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Motility</topic><topic>N-Cadherin</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacy</topic><topic>Protein Binding</topic><topic>Protein Stability</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal Transduction</topic><topic>Snail Family Transcription Factors</topic><topic>Snail protein</topic><topic>Stabilization</topic><topic>Transcription factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Tumor Necrosis Factor-alpha - physiology</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Ubiquitination</topic><topic>Zonula occludens-1 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hao</creatorcontrib><creatorcontrib>Wang, Hong-Sheng</creatorcontrib><creatorcontrib>Zhou, Bin-Hua</creatorcontrib><creatorcontrib>Li, Cui-Lin</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Wang, Xian-Feng</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>Bu, Xian-Zhang</creatorcontrib><creatorcontrib>Cai, Shao-Hui</creatorcontrib><creatorcontrib>Du, Jun</creatorcontrib><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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & 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 & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & 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 & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & 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 & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</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>Wang, Hao</au><au>Wang, Hong-Sheng</au><au>Zhou, Bin-Hua</au><au>Li, Cui-Lin</au><au>Zhang, Fan</au><au>Wang, Xian-Feng</au><au>Zhang, Ge</au><au>Bu, Xian-Zhang</au><au>Cai, Shao-Hui</au><au>Du, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-02-19</date><risdate>2013</risdate><volume>8</volume><issue>2</issue><spage>e56664</spage><epage>e56664</epage><pages>e56664-e56664</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23431386</pmid><doi>10.1371/journal.pone.0056664</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-02, Vol.8 (2), p.e56664-e56664 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330882282 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | AKT protein Biology Breast cancer Caco-2 Cells Cancer Cell adhesion & migration Cell Movement Colorectal cancer Colorectal carcinoma Colorectal Neoplasms Cytokines E-cadherin Epithelial-Mesenchymal Transition Fibronectin Gene expression Gene Knockdown Techniques Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta HCT116 Cells Humans Inflammation Kinases Localization Lymphatic system Medical research Medicine Mesenchyme Metastases Metastasis Motility N-Cadherin Pharmaceutical sciences Pharmacy Protein Binding Protein Stability Proteins Proto-Oncogene Proteins c-akt - metabolism RNA, Small Interfering - genetics Signal Transduction Snail Family Transcription Factors Snail protein Stabilization Transcription factors Transcription Factors - genetics Transcription Factors - metabolism Tumor Necrosis Factor-alpha - physiology Tumor necrosis factor-TNF Tumor necrosis factor-α Ubiquitination Zonula occludens-1 protein |
| title | Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T15%3A39%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Epithelial-mesenchymal%20transition%20(EMT)%20induced%20by%20TNF-%CE%B1%20requires%20AKT/GSK-3%CE%B2-mediated%20stabilization%20of%20snail%20in%20colorectal%20cancer&rft.jtitle=PloS%20one&rft.au=Wang,%20Hao&rft.date=2013-02-19&rft.volume=8&rft.issue=2&rft.spage=e56664&rft.epage=e56664&rft.pages=e56664-e56664&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0056664&rft_dat=%3Cproquest_plos_%3E2949773261%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330882282&rft_id=info:pmid/23431386&rft_doaj_id=oai_doaj_org_article_f57e1735af504ec3ae6e6a5441cf0d84&rfr_iscdi=true |