CEMIP, a novel adaptor protein of OGT, promotes colorectal cancer metastasis through glutamine metabolic reprogramming via reciprocal regulation of β-catenin
Metastasis is the leading cause of colorectal cancer (CRC)-induced death. However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel m...
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| Veröffentlicht in: | Oncogene 2021-11, Vol.40 (46), p.6443-6455 |
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| creator | Hua, Qingling Zhang, Biying Xu, Guojie Wang, Lanqing Wang, Haihong Lin, Zhenyu Yu, Dandan Ren, Jinghua Zhang, Dejun Zhao, Lei Zhang, Tao |
| description | Metastasis is the leading cause of colorectal cancer (CRC)-induced death. However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel metastasis-related protein, cell migration-inducing and hyaluronan-binding protein (CEMIP), can act as a novel adaptor protein of O-GlcNAc transferase (OGT) to promote CRC metastasis through glutamine metabolic reprogramming. Mechanistically, CEMIP interacts with OGT and β-catenin, which leads to elevated O-GlcNAcylation of β-catenin and enhanced β-catenin nuclear translocation from cytomembrane. Furthermore, accumulated β-catenin in nucleus enhances the transcription of CEMIP to reciprocally regulate β-catenin and contributes to over-expression of glutaminase 1 and glutamine transporters (SLC1A5 and SLC38A2). Combinational inhibition of CEMIP and glutamine metabolism could dramatically attenuate the metastasis of CRC in vivo. Collectively, this study reveals the importance of glutamine metabolic reprogramming in CEMIP-induced CRC metastasis, indicating the great potential of CEMIP and glutamine metabolism for CRC metastasis prevention. |
| doi_str_mv | 10.1038/s41388-021-02023-w |
| format | Article |
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However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel metastasis-related protein, cell migration-inducing and hyaluronan-binding protein (CEMIP), can act as a novel adaptor protein of O-GlcNAc transferase (OGT) to promote CRC metastasis through glutamine metabolic reprogramming. Mechanistically, CEMIP interacts with OGT and β-catenin, which leads to elevated O-GlcNAcylation of β-catenin and enhanced β-catenin nuclear translocation from cytomembrane. Furthermore, accumulated β-catenin in nucleus enhances the transcription of CEMIP to reciprocally regulate β-catenin and contributes to over-expression of glutaminase 1 and glutamine transporters (SLC1A5 and SLC38A2). Combinational inhibition of CEMIP and glutamine metabolism could dramatically attenuate the metastasis of CRC in vivo. Collectively, this study reveals the importance of glutamine metabolic reprogramming in CEMIP-induced CRC metastasis, indicating the great potential of CEMIP and glutamine metabolism for CRC metastasis prevention.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-021-02023-w</identifier><identifier>PMID: 34608265</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/109 ; 13/51 ; 13/89 ; 14/19 ; 38/77 ; 631/67/322 ; 631/80/86 ; 64/60 ; 82/29 ; 82/51 ; 82/83 ; Amino Acid Transport System A - metabolism ; Amino Acid Transport System ASC - metabolism ; Animals ; Apoptosis ; beta Catenin - metabolism ; Cancer ; Cell Biology ; Cell Line, Tumor ; Cell migration ; Cell Nucleus - metabolism ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Female ; Gene Expression Regulation, Neoplastic ; Glutaminase ; Glutamine ; Glutamine - metabolism ; HCT116 Cells ; Human Genetics ; Humans ; Hyaluronic acid ; Hyaluronoglucosaminidase - genetics ; Hyaluronoglucosaminidase - metabolism ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolism ; Metastases ; Metastasis ; Mice ; Minor Histocompatibility Antigens - metabolism ; Molecular modelling ; N-Acetylglucosaminyltransferases - metabolism ; Neoplasm Metastasis ; Neoplasm Transplantation ; Nuclear transport ; O-GlcNAcylation ; Oncology ; Overexpression ; Proteins ; Transcription ; Transcription, Genetic ; β-Catenin</subject><ispartof>Oncogene, 2021-11, Vol.40 (46), p.6443-6455</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-b7658e3a6ad13dad2fe7237d973069527ef5b8df2aa7d54ffde1576be813d9d53</citedby><cites>FETCH-LOGICAL-c375t-b7658e3a6ad13dad2fe7237d973069527ef5b8df2aa7d54ffde1576be813d9d53</cites><orcidid>0000-0003-2876-4347 ; 0000-0003-4018-3393 ; 0000-0002-4708-987X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34608265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hua, Qingling</creatorcontrib><creatorcontrib>Zhang, Biying</creatorcontrib><creatorcontrib>Xu, Guojie</creatorcontrib><creatorcontrib>Wang, Lanqing</creatorcontrib><creatorcontrib>Wang, Haihong</creatorcontrib><creatorcontrib>Lin, Zhenyu</creatorcontrib><creatorcontrib>Yu, Dandan</creatorcontrib><creatorcontrib>Ren, Jinghua</creatorcontrib><creatorcontrib>Zhang, Dejun</creatorcontrib><creatorcontrib>Zhao, Lei</creatorcontrib><creatorcontrib>Zhang, Tao</creatorcontrib><title>CEMIP, a novel adaptor protein of OGT, promotes colorectal cancer metastasis through glutamine metabolic reprogramming via reciprocal regulation of β-catenin</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Metastasis is the leading cause of colorectal cancer (CRC)-induced death. However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel metastasis-related protein, cell migration-inducing and hyaluronan-binding protein (CEMIP), can act as a novel adaptor protein of O-GlcNAc transferase (OGT) to promote CRC metastasis through glutamine metabolic reprogramming. Mechanistically, CEMIP interacts with OGT and β-catenin, which leads to elevated O-GlcNAcylation of β-catenin and enhanced β-catenin nuclear translocation from cytomembrane. Furthermore, accumulated β-catenin in nucleus enhances the transcription of CEMIP to reciprocally regulate β-catenin and contributes to over-expression of glutaminase 1 and glutamine transporters (SLC1A5 and SLC38A2). Combinational inhibition of CEMIP and glutamine metabolism could dramatically attenuate the metastasis of CRC in vivo. Collectively, this study reveals the importance of glutamine metabolic reprogramming in CEMIP-induced CRC metastasis, indicating the great potential of CEMIP and glutamine metabolism for CRC metastasis prevention.</description><subject>13/1</subject><subject>13/109</subject><subject>13/51</subject><subject>13/89</subject><subject>14/19</subject><subject>38/77</subject><subject>631/67/322</subject><subject>631/80/86</subject><subject>64/60</subject><subject>82/29</subject><subject>82/51</subject><subject>82/83</subject><subject>Amino Acid Transport System A - metabolism</subject><subject>Amino Acid Transport System ASC - metabolism</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>beta Catenin - metabolism</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Nucleus - metabolism</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - 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Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hua, Qingling</au><au>Zhang, Biying</au><au>Xu, Guojie</au><au>Wang, Lanqing</au><au>Wang, Haihong</au><au>Lin, Zhenyu</au><au>Yu, Dandan</au><au>Ren, Jinghua</au><au>Zhang, Dejun</au><au>Zhao, Lei</au><au>Zhang, Tao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CEMIP, a novel adaptor protein of OGT, promotes colorectal cancer metastasis through glutamine metabolic reprogramming via reciprocal regulation of β-catenin</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2021-11-18</date><risdate>2021</risdate><volume>40</volume><issue>46</issue><spage>6443</spage><epage>6455</epage><pages>6443-6455</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Metastasis is the leading cause of colorectal cancer (CRC)-induced death. However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel metastasis-related protein, cell migration-inducing and hyaluronan-binding protein (CEMIP), can act as a novel adaptor protein of O-GlcNAc transferase (OGT) to promote CRC metastasis through glutamine metabolic reprogramming. Mechanistically, CEMIP interacts with OGT and β-catenin, which leads to elevated O-GlcNAcylation of β-catenin and enhanced β-catenin nuclear translocation from cytomembrane. Furthermore, accumulated β-catenin in nucleus enhances the transcription of CEMIP to reciprocally regulate β-catenin and contributes to over-expression of glutaminase 1 and glutamine transporters (SLC1A5 and SLC38A2). Combinational inhibition of CEMIP and glutamine metabolism could dramatically attenuate the metastasis of CRC in vivo. Collectively, this study reveals the importance of glutamine metabolic reprogramming in CEMIP-induced CRC metastasis, indicating the great potential of CEMIP and glutamine metabolism for CRC metastasis prevention.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34608265</pmid><doi>10.1038/s41388-021-02023-w</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2876-4347</orcidid><orcidid>https://orcid.org/0000-0003-4018-3393</orcidid><orcidid>https://orcid.org/0000-0002-4708-987X</orcidid></addata></record> |
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| ispartof | Oncogene, 2021-11, Vol.40 (46), p.6443-6455 |
| issn | 0950-9232 1476-5594 |
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| subjects | 13/1 13/109 13/51 13/89 14/19 38/77 631/67/322 631/80/86 64/60 82/29 82/51 82/83 Amino Acid Transport System A - metabolism Amino Acid Transport System ASC - metabolism Animals Apoptosis beta Catenin - metabolism Cancer Cell Biology Cell Line, Tumor Cell migration Cell Nucleus - metabolism Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Female Gene Expression Regulation, Neoplastic Glutaminase Glutamine Glutamine - metabolism HCT116 Cells Human Genetics Humans Hyaluronic acid Hyaluronoglucosaminidase - genetics Hyaluronoglucosaminidase - metabolism Internal Medicine Medicine Medicine & Public Health Metabolism Metastases Metastasis Mice Minor Histocompatibility Antigens - metabolism Molecular modelling N-Acetylglucosaminyltransferases - metabolism Neoplasm Metastasis Neoplasm Transplantation Nuclear transport O-GlcNAcylation Oncology Overexpression Proteins Transcription Transcription, Genetic β-Catenin |
| title | CEMIP, a novel adaptor protein of OGT, promotes colorectal cancer metastasis through glutamine metabolic reprogramming via reciprocal regulation of β-catenin |
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