TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ
Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulat...
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| Veröffentlicht in: | Oncogene 2020-04, Vol.39 (18), p.3710-3725 |
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| creator | Zhou, Sha Liu, Shiliang Lin, Chuyong Li, Yue Ye, Liping Wu, Xianqiu Jian, Yunting Dai, Yuhu Ouyang, Ying Zhao, Lei Liu, Mengzhong Song, Libing Xi, Mian |
| description | Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistance in ESCC. TRIB3 is overexpressed in ESCC tissues and cell lines. High expression of TRIB3 significantly correlates with poor radiotherapy response and prognosis in ESCC patients. Upregulation of TRIB3 in ESCC cells conferred radioresistance in vitro and in vivo by interacting with TAZ thus impeding β-TrCP-mediated TAZ ubiquitination and degradation. Conversely, silencing TRIB3 sensitized ESCC cells to ionizing radiation. More importantly, TRIB3 was significantly correlated with TAZ activation in ESCC biopsies, and patients with high expression of both TRIB3 and TAZ suffered the worst radiotherapy response and survival. Our study uncovers the critical mechanism of ESCC resistance to radiotherapy, and provides a new pharmacological opportunity for developing a mechanism-based strategy to eliminate radioresistant ESCC in clinical practice. |
| doi_str_mv | 10.1038/s41388-020-1245-0 |
| format | Article |
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Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistance in ESCC. TRIB3 is overexpressed in ESCC tissues and cell lines. High expression of TRIB3 significantly correlates with poor radiotherapy response and prognosis in ESCC patients. Upregulation of TRIB3 in ESCC cells conferred radioresistance in vitro and in vivo by interacting with TAZ thus impeding β-TrCP-mediated TAZ ubiquitination and degradation. Conversely, silencing TRIB3 sensitized ESCC cells to ionizing radiation. More importantly, TRIB3 was significantly correlated with TAZ activation in ESCC biopsies, and patients with high expression of both TRIB3 and TAZ suffered the worst radiotherapy response and survival. Our study uncovers the critical mechanism of ESCC resistance to radiotherapy, and provides a new pharmacological opportunity for developing a mechanism-based strategy to eliminate radioresistant ESCC in clinical practice.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-020-1245-0</identifier><identifier>PMID: 32157210</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/100 ; 13/31 ; 13/89 ; 13/95 ; 14 ; 14/63 ; 38 ; 38/109 ; 38/77 ; 631/67/1504/1477 ; 64/60 ; 692/53/2423 ; 82/1 ; 82/51 ; 82/80 ; 82/83 ; 96/2 ; Animals ; Apoptosis ; Cell Biology ; Cell Cycle Proteins - genetics ; Disease-Free Survival ; Esophageal cancer ; Esophageal Squamous Cell Carcinoma - genetics ; Esophageal Squamous Cell Carcinoma - pathology ; Esophageal Squamous Cell Carcinoma - radiotherapy ; Esophagus ; Female ; Gene Expression Regulation, Neoplastic - radiation effects ; HEK293 Cells ; Heterografts ; Human Genetics ; Humans ; Internal Medicine ; Ionizing radiation ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Mice ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - pathology ; Neoplasm Recurrence, Local - radiotherapy ; Oncology ; Patients ; Prognosis ; Protein Binding - genetics ; Protein Serine-Threonine Kinases - antagonists & inhibitors ; Protein Serine-Threonine Kinases - genetics ; Proteolysis - radiation effects ; Radiation therapy ; Radiation Tolerance - genetics ; Radiation-Sensitizing Agents - pharmacology ; Radioresistance ; Radiotherapy ; Repressor Proteins - genetics ; Signal Transduction - genetics ; Squamous cell carcinoma ; Trans-Activators - genetics ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; Ubiquitination ; Ubiquitination - radiation effects</subject><ispartof>Oncogene, 2020-04, Vol.39 (18), p.3710-3725</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-161992b86a83ce0a26e6cf1ecb53cfb1418e79ccfff1d5d666dba8e95eca4f2f3</citedby><cites>FETCH-LOGICAL-c467t-161992b86a83ce0a26e6cf1ecb53cfb1418e79ccfff1d5d666dba8e95eca4f2f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41388-020-1245-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41388-020-1245-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32157210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Sha</creatorcontrib><creatorcontrib>Liu, Shiliang</creatorcontrib><creatorcontrib>Lin, Chuyong</creatorcontrib><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Ye, Liping</creatorcontrib><creatorcontrib>Wu, Xianqiu</creatorcontrib><creatorcontrib>Jian, Yunting</creatorcontrib><creatorcontrib>Dai, Yuhu</creatorcontrib><creatorcontrib>Ouyang, Ying</creatorcontrib><creatorcontrib>Zhao, Lei</creatorcontrib><creatorcontrib>Liu, Mengzhong</creatorcontrib><creatorcontrib>Song, Libing</creatorcontrib><creatorcontrib>Xi, Mian</creatorcontrib><title>TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistance in ESCC. TRIB3 is overexpressed in ESCC tissues and cell lines. High expression of TRIB3 significantly correlates with poor radiotherapy response and prognosis in ESCC patients. Upregulation of TRIB3 in ESCC cells conferred radioresistance in vitro and in vivo by interacting with TAZ thus impeding β-TrCP-mediated TAZ ubiquitination and degradation. Conversely, silencing TRIB3 sensitized ESCC cells to ionizing radiation. More importantly, TRIB3 was significantly correlated with TAZ activation in ESCC biopsies, and patients with high expression of both TRIB3 and TAZ suffered the worst radiotherapy response and survival. Our study uncovers the critical mechanism of ESCC resistance to radiotherapy, and provides a new pharmacological opportunity for developing a mechanism-based strategy to eliminate radioresistant ESCC in clinical practice.</description><subject>13</subject><subject>13/100</subject><subject>13/31</subject><subject>13/89</subject><subject>13/95</subject><subject>14</subject><subject>14/63</subject><subject>38</subject><subject>38/109</subject><subject>38/77</subject><subject>631/67/1504/1477</subject><subject>64/60</subject><subject>692/53/2423</subject><subject>82/1</subject><subject>82/51</subject><subject>82/80</subject><subject>82/83</subject><subject>96/2</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Biology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Disease-Free Survival</subject><subject>Esophageal cancer</subject><subject>Esophageal Squamous Cell Carcinoma - genetics</subject><subject>Esophageal Squamous Cell Carcinoma - pathology</subject><subject>Esophageal Squamous Cell Carcinoma - radiotherapy</subject><subject>Esophagus</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - radiation effects</subject><subject>HEK293 Cells</subject><subject>Heterografts</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Ionizing radiation</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm Recurrence, Local - radiotherapy</subject><subject>Oncology</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Protein Binding - genetics</subject><subject>Protein Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein Serine-Threonine Kinases - genetics</subject><subject>Proteolysis - radiation effects</subject><subject>Radiation therapy</subject><subject>Radiation Tolerance - 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antagonists & inhibitors</topic><topic>Protein Serine-Threonine Kinases - genetics</topic><topic>Proteolysis - radiation effects</topic><topic>Radiation therapy</topic><topic>Radiation Tolerance - genetics</topic><topic>Radiation-Sensitizing Agents - pharmacology</topic><topic>Radioresistance</topic><topic>Radiotherapy</topic><topic>Repressor Proteins - genetics</topic><topic>Signal Transduction - genetics</topic><topic>Squamous cell carcinoma</topic><topic>Trans-Activators - genetics</topic><topic>Transcriptional Coactivator with PDZ-Binding Motif Proteins</topic><topic>Ubiquitination</topic><topic>Ubiquitination - radiation effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Sha</creatorcontrib><creatorcontrib>Liu, Shiliang</creatorcontrib><creatorcontrib>Lin, Chuyong</creatorcontrib><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Ye, Liping</creatorcontrib><creatorcontrib>Wu, Xianqiu</creatorcontrib><creatorcontrib>Jian, Yunting</creatorcontrib><creatorcontrib>Dai, Yuhu</creatorcontrib><creatorcontrib>Ouyang, Ying</creatorcontrib><creatorcontrib>Zhao, Lei</creatorcontrib><creatorcontrib>Liu, Mengzhong</creatorcontrib><creatorcontrib>Song, Libing</creatorcontrib><creatorcontrib>Xi, Mian</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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</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 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</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>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Sha</au><au>Liu, Shiliang</au><au>Lin, Chuyong</au><au>Li, Yue</au><au>Ye, Liping</au><au>Wu, Xianqiu</au><au>Jian, Yunting</au><au>Dai, Yuhu</au><au>Ouyang, Ying</au><au>Zhao, Lei</au><au>Liu, Mengzhong</au><au>Song, Libing</au><au>Xi, Mian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2020-04-30</date><risdate>2020</risdate><volume>39</volume><issue>18</issue><spage>3710</spage><epage>3725</epage><pages>3710-3725</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistance in ESCC. TRIB3 is overexpressed in ESCC tissues and cell lines. High expression of TRIB3 significantly correlates with poor radiotherapy response and prognosis in ESCC patients. Upregulation of TRIB3 in ESCC cells conferred radioresistance in vitro and in vivo by interacting with TAZ thus impeding β-TrCP-mediated TAZ ubiquitination and degradation. Conversely, silencing TRIB3 sensitized ESCC cells to ionizing radiation. More importantly, TRIB3 was significantly correlated with TAZ activation in ESCC biopsies, and patients with high expression of both TRIB3 and TAZ suffered the worst radiotherapy response and survival. Our study uncovers the critical mechanism of ESCC resistance to radiotherapy, and provides a new pharmacological opportunity for developing a mechanism-based strategy to eliminate radioresistant ESCC in clinical practice.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32157210</pmid><doi>10.1038/s41388-020-1245-0</doi><tpages>16</tpages></addata></record> |
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| subjects | 13 13/100 13/31 13/89 13/95 14 14/63 38 38/109 38/77 631/67/1504/1477 64/60 692/53/2423 82/1 82/51 82/80 82/83 96/2 Animals Apoptosis Cell Biology Cell Cycle Proteins - genetics Disease-Free Survival Esophageal cancer Esophageal Squamous Cell Carcinoma - genetics Esophageal Squamous Cell Carcinoma - pathology Esophageal Squamous Cell Carcinoma - radiotherapy Esophagus Female Gene Expression Regulation, Neoplastic - radiation effects HEK293 Cells Heterografts Human Genetics Humans Internal Medicine Ionizing radiation Male Medical prognosis Medicine Medicine & Public Health Mice Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - pathology Neoplasm Recurrence, Local - radiotherapy Oncology Patients Prognosis Protein Binding - genetics Protein Serine-Threonine Kinases - antagonists & inhibitors Protein Serine-Threonine Kinases - genetics Proteolysis - radiation effects Radiation therapy Radiation Tolerance - genetics Radiation-Sensitizing Agents - pharmacology Radioresistance Radiotherapy Repressor Proteins - genetics Signal Transduction - genetics Squamous cell carcinoma Trans-Activators - genetics Transcriptional Coactivator with PDZ-Binding Motif Proteins Ubiquitination Ubiquitination - radiation effects |
| title | TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ |
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