A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma
Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, theref...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2020-02, Vol.11 (2), p.89-89, Article 89 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 89 |
|---|---|
| container_issue | 2 |
| container_start_page | 89 |
| container_title | Cell death & disease |
| container_volume | 11 |
| creator | Feng, Yilu Zhang, Ye Cai, Yi Liu, Ruijie Lu, Miaolong Li, Tangzhiming Fu, Ying Guo, Ming Huang, Huichao Ou, Yifu Chen, Yongheng |
| description | Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment. |
| doi_str_mv | 10.1038/s41419-020-2278-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_32015333</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2350904534</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-1ea44f4709fc77dc4c8a656e8a0236900f08f4e8eb77726a47bb87d121a689b43</originalsourceid><addsrcrecordid>eNqNkV9rFDEUxQdRbKn9AL5IwBdBxubfJJkXoSxWxQX7oL6GTPbObMpssiYZZb-9GaeurSA0L7mQ37k5h1NVzwl-QzBTF4kTTtoaU1xTKlUtHlWnFHNSc6Xax3fmk-o8pRtcDmOYNuJpdcIoJg1j7LT6dkkxyiYOkBO6vvq0RsZv0DAebBgPySWUA3J-6zqXUd4C2scwREjJBY9Cj7awNzlYGMdpNBFZE63zYWeeVU96MyY4v73Pqq9X776sPtTrz-8_ri7XtW2YyDUBw3nPJW57K-XGcquMaAQogykTLcY9Vj0HBZ2UkgrDZdcpuSGUGKHajrOz6u2ydz91O9hY8DmaUe-j25l40ME4ff_Fu60ewg8t2lYyIcqCV7cLYvg-Qcp659Kcx3gIU9KUNbjFvGHzXy__QW_CFH2J95tiVBXrhSILZWNIKUJ_NEOwnovTS3G6FKfn4vSseXE3xVHxp6YCqAX4CV3ok3XgLRyx0mxDCGsVKRMhK5dNLv2swuRzkb5-uLTQdKFTIfwA8W_G_9v_BTjAw5M</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2350328656</pqid></control><display><type>article</type><title>A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><creator>Feng, Yilu ; Zhang, Ye ; Cai, Yi ; Liu, Ruijie ; Lu, Miaolong ; Li, Tangzhiming ; Fu, Ying ; Guo, Ming ; Huang, Huichao ; Ou, Yifu ; Chen, Yongheng</creator><creatorcontrib>Feng, Yilu ; Zhang, Ye ; Cai, Yi ; Liu, Ruijie ; Lu, Miaolong ; Li, Tangzhiming ; Fu, Ying ; Guo, Ming ; Huang, Huichao ; Ou, Yifu ; Chen, Yongheng</creatorcontrib><description>Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-020-2278-6</identifier><identifier>PMID: 32015333</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/109 ; 13/21 ; 13/44 ; 13/51 ; 13/89 ; 14/19 ; 14/35 ; 14/63 ; 38/77 ; 45/29 ; 631/45 ; 631/67/2327 ; 64/60 ; 82/83 ; Animals ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Cell Biology ; Cell Culture ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell Proliferation ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Glucose - metabolism ; Glycolysis ; Hepatocellular carcinoma ; Humans ; Immunology ; Life Sciences ; Life Sciences & Biomedicine ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Mice ; Phosphofructokinase ; Phosphofructokinase-1, Liver Type - genetics ; Phosphofructokinase-1, Liver Type - metabolism ; Protein Binding ; RNA-mediated interference ; Science & Technology ; Therapeutic applications ; Tumor Necrosis Factor alpha-Induced Protein 3 - genetics ; Tumor Necrosis Factor alpha-Induced Protein 3 - metabolism ; Tumor suppression ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Ubiquitin ; Ubiquitin-protein ligase ; Ubiquitination ; Xenograft Model Antitumor Assays</subject><ispartof>Cell death & disease, 2020-02, Vol.11 (2), p.89-89, Article 89</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>66</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000511398100011</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c536t-1ea44f4709fc77dc4c8a656e8a0236900f08f4e8eb77726a47bb87d121a689b43</citedby><cites>FETCH-LOGICAL-c536t-1ea44f4709fc77dc4c8a656e8a0236900f08f4e8eb77726a47bb87d121a689b43</cites><orcidid>0000-0001-8139-6892 ; 0000-0001-8418-4561 ; 0000-0002-5273-9531</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997366/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997366/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2118,27933,27934,28257,41129,42198,51585,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32015333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Yilu</creatorcontrib><creatorcontrib>Zhang, Ye</creatorcontrib><creatorcontrib>Cai, Yi</creatorcontrib><creatorcontrib>Liu, Ruijie</creatorcontrib><creatorcontrib>Lu, Miaolong</creatorcontrib><creatorcontrib>Li, Tangzhiming</creatorcontrib><creatorcontrib>Fu, Ying</creatorcontrib><creatorcontrib>Guo, Ming</creatorcontrib><creatorcontrib>Huang, Huichao</creatorcontrib><creatorcontrib>Ou, Yifu</creatorcontrib><creatorcontrib>Chen, Yongheng</creatorcontrib><title>A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>CELL DEATH DIS</addtitle><addtitle>Cell Death Dis</addtitle><description>Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment.</description><subject>13/1</subject><subject>13/109</subject><subject>13/21</subject><subject>13/44</subject><subject>13/51</subject><subject>13/89</subject><subject>14/19</subject><subject>14/35</subject><subject>14/63</subject><subject>38/77</subject><subject>45/29</subject><subject>631/45</subject><subject>631/67/2327</subject><subject>64/60</subject><subject>82/83</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Disease Progression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glucose - metabolism</subject><subject>Glycolysis</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>Life Sciences & Biomedicine</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Mice</subject><subject>Phosphofructokinase</subject><subject>Phosphofructokinase-1, Liver Type - genetics</subject><subject>Phosphofructokinase-1, Liver Type - metabolism</subject><subject>Protein Binding</subject><subject>RNA-mediated interference</subject><subject>Science & Technology</subject><subject>Therapeutic applications</subject><subject>Tumor Necrosis Factor alpha-Induced Protein 3 - genetics</subject><subject>Tumor Necrosis Factor alpha-Induced Protein 3 - metabolism</subject><subject>Tumor suppression</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><subject>Ubiquitination</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkV9rFDEUxQdRbKn9AL5IwBdBxubfJJkXoSxWxQX7oL6GTPbObMpssiYZZb-9GaeurSA0L7mQ37k5h1NVzwl-QzBTF4kTTtoaU1xTKlUtHlWnFHNSc6Xax3fmk-o8pRtcDmOYNuJpdcIoJg1j7LT6dkkxyiYOkBO6vvq0RsZv0DAebBgPySWUA3J-6zqXUd4C2scwREjJBY9Cj7awNzlYGMdpNBFZE63zYWeeVU96MyY4v73Pqq9X776sPtTrz-8_ri7XtW2YyDUBw3nPJW57K-XGcquMaAQogykTLcY9Vj0HBZ2UkgrDZdcpuSGUGKHajrOz6u2ydz91O9hY8DmaUe-j25l40ME4ff_Fu60ewg8t2lYyIcqCV7cLYvg-Qcp659Kcx3gIU9KUNbjFvGHzXy__QW_CFH2J95tiVBXrhSILZWNIKUJ_NEOwnovTS3G6FKfn4vSseXE3xVHxp6YCqAX4CV3ok3XgLRyx0mxDCGsVKRMhK5dNLv2swuRzkb5-uLTQdKFTIfwA8W_G_9v_BTjAw5M</recordid><startdate>20200203</startdate><enddate>20200203</enddate><creator>Feng, Yilu</creator><creator>Zhang, Ye</creator><creator>Cai, Yi</creator><creator>Liu, Ruijie</creator><creator>Lu, Miaolong</creator><creator>Li, Tangzhiming</creator><creator>Fu, Ying</creator><creator>Guo, Ming</creator><creator>Huang, Huichao</creator><creator>Ou, Yifu</creator><creator>Chen, Yongheng</creator><general>Nature Publishing Group UK</general><general>Springer Nature</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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>88A</scope><scope>88I</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>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8139-6892</orcidid><orcidid>https://orcid.org/0000-0001-8418-4561</orcidid><orcidid>https://orcid.org/0000-0002-5273-9531</orcidid></search><sort><creationdate>20200203</creationdate><title>A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma</title><author>Feng, Yilu ; Zhang, Ye ; Cai, Yi ; Liu, Ruijie ; Lu, Miaolong ; Li, Tangzhiming ; Fu, Ying ; Guo, Ming ; Huang, Huichao ; Ou, Yifu ; Chen, Yongheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-1ea44f4709fc77dc4c8a656e8a0236900f08f4e8eb77726a47bb87d121a689b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/1</topic><topic>13/109</topic><topic>13/21</topic><topic>13/44</topic><topic>13/51</topic><topic>13/89</topic><topic>14/19</topic><topic>14/35</topic><topic>14/63</topic><topic>38/77</topic><topic>45/29</topic><topic>631/45</topic><topic>631/67/2327</topic><topic>64/60</topic><topic>82/83</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Disease Progression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glucose - metabolism</topic><topic>Glycolysis</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immunology</topic><topic>Life Sciences</topic><topic>Life Sciences & Biomedicine</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Mice</topic><topic>Phosphofructokinase</topic><topic>Phosphofructokinase-1, Liver Type - genetics</topic><topic>Phosphofructokinase-1, Liver Type - metabolism</topic><topic>Protein Binding</topic><topic>RNA-mediated interference</topic><topic>Science & Technology</topic><topic>Therapeutic applications</topic><topic>Tumor Necrosis Factor alpha-Induced Protein 3 - genetics</topic><topic>Tumor Necrosis Factor alpha-Induced Protein 3 - metabolism</topic><topic>Tumor suppression</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Ubiquitin</topic><topic>Ubiquitin-protein ligase</topic><topic>Ubiquitination</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Yilu</creatorcontrib><creatorcontrib>Zhang, Ye</creatorcontrib><creatorcontrib>Cai, Yi</creatorcontrib><creatorcontrib>Liu, Ruijie</creatorcontrib><creatorcontrib>Lu, Miaolong</creatorcontrib><creatorcontrib>Li, Tangzhiming</creatorcontrib><creatorcontrib>Fu, Ying</creatorcontrib><creatorcontrib>Guo, Ming</creatorcontrib><creatorcontrib>Huang, Huichao</creatorcontrib><creatorcontrib>Ou, Yifu</creatorcontrib><creatorcontrib>Chen, Yongheng</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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 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>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>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Yilu</au><au>Zhang, Ye</au><au>Cai, Yi</au><au>Liu, Ruijie</au><au>Lu, Miaolong</au><au>Li, Tangzhiming</au><au>Fu, Ying</au><au>Guo, Ming</au><au>Huang, Huichao</au><au>Ou, Yifu</au><au>Chen, Yongheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><stitle>CELL DEATH DIS</stitle><addtitle>Cell Death Dis</addtitle><date>2020-02-03</date><risdate>2020</risdate><volume>11</volume><issue>2</issue><spage>89</spage><epage>89</epage><pages>89-89</pages><artnum>89</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32015333</pmid><doi>10.1038/s41419-020-2278-6</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-8139-6892</orcidid><orcidid>https://orcid.org/0000-0001-8418-4561</orcidid><orcidid>https://orcid.org/0000-0002-5273-9531</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2020-02, Vol.11 (2), p.89-89, Article 89 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmed_primary_32015333 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA/Free Journals |
| subjects | 13/1 13/109 13/21 13/44 13/51 13/89 14/19 14/35 14/63 38/77 45/29 631/45 631/67/2327 64/60 82/83 Animals Antibodies Biochemistry Biomedical and Life Sciences Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Cell Biology Cell Culture Cell Line, Tumor Cell migration Cell Movement Cell Proliferation Disease Progression Gene Expression Regulation, Neoplastic Glucose - metabolism Glycolysis Hepatocellular carcinoma Humans Immunology Life Sciences Life Sciences & Biomedicine Liver cancer Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Mice Phosphofructokinase Phosphofructokinase-1, Liver Type - genetics Phosphofructokinase-1, Liver Type - metabolism Protein Binding RNA-mediated interference Science & Technology Therapeutic applications Tumor Necrosis Factor alpha-Induced Protein 3 - genetics Tumor Necrosis Factor alpha-Induced Protein 3 - metabolism Tumor suppression Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Ubiquitin Ubiquitin-protein ligase Ubiquitination Xenograft Model Antitumor Assays |
| title | A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-30T22%3A01%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A20%20targets%20PFKL%20and%20glycolysis%20to%20inhibit%20the%20progression%20of%20hepatocellular%20carcinoma&rft.jtitle=Cell%20death%20&%20disease&rft.au=Feng,%20Yilu&rft.date=2020-02-03&rft.volume=11&rft.issue=2&rft.spage=89&rft.epage=89&rft.pages=89-89&rft.artnum=89&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-020-2278-6&rft_dat=%3Cproquest_pubme%3E2350904534%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2350328656&rft_id=info:pmid/32015333&rfr_iscdi=true |