Activating CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer
Hypoxia, or the deficiency of oxygen, in solid tumors is majorly responsible for the progression of cancer and remains unaffected by chemotherapy, but still requires definitive definition of the hypoxia signaling. Hypoxia disrupts the complete folding of mitochondrial proteins, leading to several di...
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| Veröffentlicht in: | Oncogene 2020-01, Vol.39 (1), p.136-150 |
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| creator | Park, Seong Hye Jeong, Soyeon Kim, Bo Ram Jeong, Yoon A Kim, Jung Lim Na, Yoo Jin Jo, Min Jee Yun, Hye Kyeong Kim, Dae Yeong Kim, Bu Gyeom Lee, Dae-Hee Oh, Sang Cheul |
| description | Hypoxia, or the deficiency of oxygen, in solid tumors is majorly responsible for the progression of cancer and remains unaffected by chemotherapy, but still requires definitive definition of the hypoxia signaling. Hypoxia disrupts the complete folding of mitochondrial proteins, leading to several diseases. The present study confirms that hypoxia activates the Hedgehog pathway in colorectal cancer (CRC), considering its role in cancer epithelial to mesenchymal transition, migration, and invasion. The activity of hypoxia-mediated Gli-1, a Hedgehog signaling factor in hypoxia, was confirmed by in vitro western blotting, immunofluorescence staining, wound-healing assay, and matrigel invasion assay, as well as by in vivo xenograft models (
n
= 5 per group). The Gli-1 mechanism in hypoxia was analyzed via mass spectrometry. Hypoxia enhanced the interaction of Gli-1 and T-complex protein 1 subunit beta (CCT2), as observed in the mass spectrometric analysis. We observed that reduction in CCT2 inhibits tumor induction by Gli-1. Ubiquitination-mediated Gli-1 degradation by β-TrCP occurs during incomplete folding of Gli-1 in hypoxia. The human CRC tissues revealed greater CCT2 expression than did the normal colon tissues, indicating that higher CCT2 expression in tumor tissues from CRC patients reduced their survival rate. Moreover, we suggest that CCT2 correlates with Gli-1 expression and is an important determinant of survival in the CRC patients. The results reveal that CCT2 can regulate the folding of Gli-1 in relation to hypoxia in CRC. |
| doi_str_mv | 10.1038/s41388-019-0972-6 |
| format | Article |
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n
= 5 per group). The Gli-1 mechanism in hypoxia was analyzed via mass spectrometry. Hypoxia enhanced the interaction of Gli-1 and T-complex protein 1 subunit beta (CCT2), as observed in the mass spectrometric analysis. We observed that reduction in CCT2 inhibits tumor induction by Gli-1. Ubiquitination-mediated Gli-1 degradation by β-TrCP occurs during incomplete folding of Gli-1 in hypoxia. The human CRC tissues revealed greater CCT2 expression than did the normal colon tissues, indicating that higher CCT2 expression in tumor tissues from CRC patients reduced their survival rate. Moreover, we suggest that CCT2 correlates with Gli-1 expression and is an important determinant of survival in the CRC patients. The results reveal that CCT2 can regulate the folding of Gli-1 in relation to hypoxia in CRC.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-019-0972-6</identifier><identifier>PMID: 31462707</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/322 ; 631/67/395 ; 631/80/82/23 ; 82/1 ; 82/29 ; 82/51 ; 82/58 ; 96/31 ; Analysis ; Animals ; Apoptosis ; beta-Transducin Repeat-Containing Proteins - pharmacology ; Cancer ; Care and treatment ; Cell Biology ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Chaperonin Containing TCP-1 - chemistry ; Chaperonin Containing TCP-1 - genetics ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Development and progression ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; HCT116 Cells ; Hedgehog protein ; Hedgehog Proteins - genetics ; Heterografts ; Human Genetics ; Humans ; Hypoxia ; Immunofluorescence ; Internal Medicine ; Male ; Mass spectrometry ; Mass spectroscopy ; Medicine ; Medicine & Public Health ; Mesenchyme ; Mice ; Mitochondria ; Neoplasm Invasiveness - genetics ; Neoplasm Invasiveness - pathology ; Oncology ; Protein Folding ; Proteins ; Proteolysis - drug effects ; Signal Transduction - genetics ; Solid tumors ; Survival ; Survival Rate ; Tumor Hypoxia - genetics ; Ubiquitination ; Ubiquitination - genetics ; Western blotting ; Wound healing ; Xenografts ; Zinc Finger Protein GLI1 - chemistry ; Zinc Finger Protein GLI1 - genetics</subject><ispartof>Oncogene, 2020-01, Vol.39 (1), p.136-150</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2020</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-eeb9958095365cd8daa350a2e9e0f14dd69ca09abe5e640579f0489ccfce5f453</citedby><cites>FETCH-LOGICAL-c533t-eeb9958095365cd8daa350a2e9e0f14dd69ca09abe5e640579f0489ccfce5f453</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/s41388-019-0972-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41388-019-0972-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31462707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Seong Hye</creatorcontrib><creatorcontrib>Jeong, Soyeon</creatorcontrib><creatorcontrib>Kim, Bo Ram</creatorcontrib><creatorcontrib>Jeong, Yoon A</creatorcontrib><creatorcontrib>Kim, Jung Lim</creatorcontrib><creatorcontrib>Na, Yoo Jin</creatorcontrib><creatorcontrib>Jo, Min Jee</creatorcontrib><creatorcontrib>Yun, Hye Kyeong</creatorcontrib><creatorcontrib>Kim, Dae Yeong</creatorcontrib><creatorcontrib>Kim, Bu Gyeom</creatorcontrib><creatorcontrib>Lee, Dae-Hee</creatorcontrib><creatorcontrib>Oh, Sang Cheul</creatorcontrib><title>Activating CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Hypoxia, or the deficiency of oxygen, in solid tumors is majorly responsible for the progression of cancer and remains unaffected by chemotherapy, but still requires definitive definition of the hypoxia signaling. Hypoxia disrupts the complete folding of mitochondrial proteins, leading to several diseases. The present study confirms that hypoxia activates the Hedgehog pathway in colorectal cancer (CRC), considering its role in cancer epithelial to mesenchymal transition, migration, and invasion. The activity of hypoxia-mediated Gli-1, a Hedgehog signaling factor in hypoxia, was confirmed by in vitro western blotting, immunofluorescence staining, wound-healing assay, and matrigel invasion assay, as well as by in vivo xenograft models (
n
= 5 per group). The Gli-1 mechanism in hypoxia was analyzed via mass spectrometry. Hypoxia enhanced the interaction of Gli-1 and T-complex protein 1 subunit beta (CCT2), as observed in the mass spectrometric analysis. We observed that reduction in CCT2 inhibits tumor induction by Gli-1. Ubiquitination-mediated Gli-1 degradation by β-TrCP occurs during incomplete folding of Gli-1 in hypoxia. The human CRC tissues revealed greater CCT2 expression than did the normal colon tissues, indicating that higher CCT2 expression in tumor tissues from CRC patients reduced their survival rate. Moreover, we suggest that CCT2 correlates with Gli-1 expression and is an important determinant of survival in the CRC patients. The results reveal that CCT2 can regulate the folding of Gli-1 in relation to hypoxia in CRC.</description><subject>631/67/322</subject><subject>631/67/395</subject><subject>631/80/82/23</subject><subject>82/1</subject><subject>82/29</subject><subject>82/51</subject><subject>82/58</subject><subject>96/31</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>beta-Transducin Repeat-Containing Proteins - pharmacology</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Chaperonin Containing TCP-1 - chemistry</subject><subject>Chaperonin Containing TCP-1 - genetics</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Development and progression</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>HCT116 Cells</subject><subject>Hedgehog protein</subject><subject>Hedgehog Proteins - genetics</subject><subject>Heterografts</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunofluorescence</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Oncology</subject><subject>Protein Folding</subject><subject>Proteins</subject><subject>Proteolysis - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Solid tumors</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Tumor Hypoxia - genetics</subject><subject>Ubiquitination</subject><subject>Ubiquitination - genetics</subject><subject>Western blotting</subject><subject>Wound healing</subject><subject>Xenografts</subject><subject>Zinc Finger Protein GLI1 - chemistry</subject><subject>Zinc Finger Protein GLI1 - 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CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer</title><author>Park, Seong Hye ; Jeong, Soyeon ; Kim, Bo Ram ; Jeong, Yoon A ; Kim, Jung Lim ; Na, Yoo Jin ; Jo, Min Jee ; Yun, Hye Kyeong ; Kim, Dae Yeong ; Kim, Bu Gyeom ; Lee, Dae-Hee ; Oh, Sang Cheul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-eeb9958095365cd8daa350a2e9e0f14dd69ca09abe5e640579f0489ccfce5f453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/67/322</topic><topic>631/67/395</topic><topic>631/80/82/23</topic><topic>82/1</topic><topic>82/29</topic><topic>82/51</topic><topic>82/58</topic><topic>96/31</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>beta-Transducin Repeat-Containing Proteins - pharmacology</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Chaperonin Containing TCP-1 - chemistry</topic><topic>Chaperonin Containing TCP-1 - genetics</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Development and progression</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>HCT116 Cells</topic><topic>Hedgehog protein</topic><topic>Hedgehog Proteins - genetics</topic><topic>Heterografts</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Immunofluorescence</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Oncology</topic><topic>Protein Folding</topic><topic>Proteins</topic><topic>Proteolysis - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Solid tumors</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Tumor Hypoxia - genetics</topic><topic>Ubiquitination</topic><topic>Ubiquitination - genetics</topic><topic>Western blotting</topic><topic>Wound healing</topic><topic>Xenografts</topic><topic>Zinc Finger Protein GLI1 - chemistry</topic><topic>Zinc Finger Protein GLI1 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Seong Hye</creatorcontrib><creatorcontrib>Jeong, Soyeon</creatorcontrib><creatorcontrib>Kim, Bo Ram</creatorcontrib><creatorcontrib>Jeong, Yoon A</creatorcontrib><creatorcontrib>Kim, Jung Lim</creatorcontrib><creatorcontrib>Na, Yoo Jin</creatorcontrib><creatorcontrib>Jo, Min 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Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Seong Hye</au><au>Jeong, Soyeon</au><au>Kim, Bo Ram</au><au>Jeong, Yoon A</au><au>Kim, Jung Lim</au><au>Na, Yoo Jin</au><au>Jo, Min Jee</au><au>Yun, Hye Kyeong</au><au>Kim, Dae Yeong</au><au>Kim, Bu Gyeom</au><au>Lee, Dae-Hee</au><au>Oh, Sang Cheul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activating CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2020-01-02</date><risdate>2020</risdate><volume>39</volume><issue>1</issue><spage>136</spage><epage>150</epage><pages>136-150</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Hypoxia, or the deficiency of oxygen, in solid tumors is majorly responsible for the progression of cancer and remains unaffected by chemotherapy, but still requires definitive definition of the hypoxia signaling. Hypoxia disrupts the complete folding of mitochondrial proteins, leading to several diseases. The present study confirms that hypoxia activates the Hedgehog pathway in colorectal cancer (CRC), considering its role in cancer epithelial to mesenchymal transition, migration, and invasion. The activity of hypoxia-mediated Gli-1, a Hedgehog signaling factor in hypoxia, was confirmed by in vitro western blotting, immunofluorescence staining, wound-healing assay, and matrigel invasion assay, as well as by in vivo xenograft models (
n
= 5 per group). The Gli-1 mechanism in hypoxia was analyzed via mass spectrometry. Hypoxia enhanced the interaction of Gli-1 and T-complex protein 1 subunit beta (CCT2), as observed in the mass spectrometric analysis. We observed that reduction in CCT2 inhibits tumor induction by Gli-1. Ubiquitination-mediated Gli-1 degradation by β-TrCP occurs during incomplete folding of Gli-1 in hypoxia. The human CRC tissues revealed greater CCT2 expression than did the normal colon tissues, indicating that higher CCT2 expression in tumor tissues from CRC patients reduced their survival rate. Moreover, we suggest that CCT2 correlates with Gli-1 expression and is an important determinant of survival in the CRC patients. The results reveal that CCT2 can regulate the folding of Gli-1 in relation to hypoxia in CRC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31462707</pmid><doi>10.1038/s41388-019-0972-6</doi><tpages>15</tpages></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 631/67/322 631/67/395 631/80/82/23 82/1 82/29 82/51 82/58 96/31 Analysis Animals Apoptosis beta-Transducin Repeat-Containing Proteins - pharmacology Cancer Care and treatment Cell Biology Cell Movement - drug effects Cell Proliferation - drug effects Chaperonin Containing TCP-1 - chemistry Chaperonin Containing TCP-1 - genetics Chemotherapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Development and progression Female Gene Expression Regulation, Neoplastic - drug effects HCT116 Cells Hedgehog protein Hedgehog Proteins - genetics Heterografts Human Genetics Humans Hypoxia Immunofluorescence Internal Medicine Male Mass spectrometry Mass spectroscopy Medicine Medicine & Public Health Mesenchyme Mice Mitochondria Neoplasm Invasiveness - genetics Neoplasm Invasiveness - pathology Oncology Protein Folding Proteins Proteolysis - drug effects Signal Transduction - genetics Solid tumors Survival Survival Rate Tumor Hypoxia - genetics Ubiquitination Ubiquitination - genetics Western blotting Wound healing Xenografts Zinc Finger Protein GLI1 - chemistry Zinc Finger Protein GLI1 - genetics |
| title | Activating CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer |
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