Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma
Cancer cells, including malignant lymphoma cells, alter their metabolism, termed “metabolic reprograming,” on initiation of malignant transformation as well as upon accumulation of genetic abnormalities. Here, to identify a novel therapeutic target involved in the metabolic changes during malignant...
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| Veröffentlicht in: | Laboratory investigation 2020-03, Vol.100 (3), p.353-362 |
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| creator | Yamamoto, Kouhei Abe, Shinya Honda, Ayaka Hashimoto, Jun Aizawa, Yuuki Ishibashi, Sachiko Takemura, Taro Hanagata, Nobutaka Yamamoto, Masahide Miura, Osamu Kurata, Morito Kitagawa, Masanobu |
| description | Cancer cells, including malignant lymphoma cells, alter their metabolism, termed “metabolic reprograming,” on initiation of malignant transformation as well as upon accumulation of genetic abnormalities. Here, to identify a novel therapeutic target involved in the metabolic changes during malignant lymphoma, we performed global analyses combined with shotgun proteomics, in silico database analysis, and clinic-pathologic analysis of nonneoplastic lymphoid tissue and malignant lymphoma tissue and verified the molecular functions in vitro. In total, 2002 proteins were detected from both samples and proteins related to fatty acid beta-oxidation (FAO) were detected more frequently in malignant lymphoma tissue. Consequently, the most frequently detected protein, the mitochondrial trifunctional enzyme subunit-alpha (HADHA), was identified as a potential target. Immunohistochemical analyses revealed that HADHA tended to be overexpressed in a high-grade subtype of malignant lymphoma tissue. Clinicopathologic study revealed that HADHA overexpression was correlated with significantly worse overall survival (P= 0.013) and was an independent prognostic predictor in diffuse large B-cell lymphoma (P= 0.027). In vitro, downregulation of HADHA negatively regulated cell growth by causing G0/G1 arrest (P= 0.0008) similar to treatment with etomoxir, an inhibitor of FAO (P= 0.032). Moreover, downregulation of HADHA increased the susceptibility to doxorubicin (P= 0.002) and etoposide (P= 0.004). Moreover, these phenotypes were confirmed in an HADHA knockout system. Thus, we provide a basis for a novel therapeutic strategy through the regulation of HADHA and FAO in patients with refractory malignant lymphoma. |
| doi_str_mv | 10.1038/s41374-019-0318-6 |
| format | Article |
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Here, to identify a novel therapeutic target involved in the metabolic changes during malignant lymphoma, we performed global analyses combined with shotgun proteomics, in silico database analysis, and clinic-pathologic analysis of nonneoplastic lymphoid tissue and malignant lymphoma tissue and verified the molecular functions in vitro. In total, 2002 proteins were detected from both samples and proteins related to fatty acid beta-oxidation (FAO) were detected more frequently in malignant lymphoma tissue. Consequently, the most frequently detected protein, the mitochondrial trifunctional enzyme subunit-alpha (HADHA), was identified as a potential target. Immunohistochemical analyses revealed that HADHA tended to be overexpressed in a high-grade subtype of malignant lymphoma tissue. Clinicopathologic study revealed that HADHA overexpression was correlated with significantly worse overall survival (P= 0.013) and was an independent prognostic predictor in diffuse large B-cell lymphoma (P= 0.027). In vitro, downregulation of HADHA negatively regulated cell growth by causing G0/G1 arrest (P= 0.0008) similar to treatment with etomoxir, an inhibitor of FAO (P= 0.032). Moreover, downregulation of HADHA increased the susceptibility to doxorubicin (P= 0.002) and etoposide (P= 0.004). Moreover, these phenotypes were confirmed in an HADHA knockout system. Thus, we provide a basis for a novel therapeutic strategy through the regulation of HADHA and FAO in patients with refractory malignant lymphoma.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/s41374-019-0318-6</identifier><identifier>PMID: 31527828</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>13/106 ; 13/109 ; 13/31 ; 13/51 ; 631/67/1059/602 ; 631/67/2327 ; 82/58 ; Abnormalities ; Antineoplastic Agents - pharmacology ; B-cell lymphoma ; Cell death ; Cell growth ; Cell Line, Tumor ; Cell Survival - drug effects ; Correlation analysis ; Down-Regulation ; Doxorubicin ; Drug Discovery ; Enzymes ; Etoposide ; Fatty acids ; Fatty Acids - metabolism ; Female ; Genetic abnormalities ; Genetic transformation ; Humans ; Laboratory Medicine ; Lymphocytes ; Lymphocytes B ; Lymphoid tissue ; Lymphoid Tissue - chemistry ; Lymphoid Tissue - metabolism ; Lymphoma ; Lymphoma - metabolism ; Lymphoma - mortality ; Lymphoma - pathology ; Male ; Medicine ; Medicine & Public Health ; Metabolic pathways ; Metabolism ; Middle Aged ; Mitochondria ; Mitochondrial Trifunctional Protein, alpha Subunit - antagonists & inhibitors ; Mitochondrial Trifunctional Protein, alpha Subunit - genetics ; Mitochondrial Trifunctional Protein, alpha Subunit - metabolism ; Oxidation ; Oxidation-Reduction ; Pathology ; Phenotypes ; Proteins ; Proteome - analysis ; Proteome - metabolism ; Proteomics ; Shotguns ; Target recognition ; Therapeutic applications ; Tissues</subject><ispartof>Laboratory investigation, 2020-03, Vol.100 (3), p.353-362</ispartof><rights>2019 United States & Canadian Academy of Pathology</rights><rights>United States & Canadian Academy of Pathology 2019</rights><rights>2019© United States & Canadian Academy of Pathology 2019</rights><rights>United States & Canadian Academy of Pathology 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-8cde561759767784a0335d7beb6505e0872f0359741d062f58fef32dc13541b83</citedby><cites>FETCH-LOGICAL-c495t-8cde561759767784a0335d7beb6505e0872f0359741d062f58fef32dc13541b83</cites></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/31527828$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamamoto, Kouhei</creatorcontrib><creatorcontrib>Abe, Shinya</creatorcontrib><creatorcontrib>Honda, Ayaka</creatorcontrib><creatorcontrib>Hashimoto, Jun</creatorcontrib><creatorcontrib>Aizawa, Yuuki</creatorcontrib><creatorcontrib>Ishibashi, Sachiko</creatorcontrib><creatorcontrib>Takemura, Taro</creatorcontrib><creatorcontrib>Hanagata, Nobutaka</creatorcontrib><creatorcontrib>Yamamoto, Masahide</creatorcontrib><creatorcontrib>Miura, Osamu</creatorcontrib><creatorcontrib>Kurata, Morito</creatorcontrib><creatorcontrib>Kitagawa, Masanobu</creatorcontrib><title>Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>Cancer cells, including malignant lymphoma cells, alter their metabolism, termed “metabolic reprograming,” on initiation of malignant transformation as well as upon accumulation of genetic abnormalities. Here, to identify a novel therapeutic target involved in the metabolic changes during malignant lymphoma, we performed global analyses combined with shotgun proteomics, in silico database analysis, and clinic-pathologic analysis of nonneoplastic lymphoid tissue and malignant lymphoma tissue and verified the molecular functions in vitro. In total, 2002 proteins were detected from both samples and proteins related to fatty acid beta-oxidation (FAO) were detected more frequently in malignant lymphoma tissue. Consequently, the most frequently detected protein, the mitochondrial trifunctional enzyme subunit-alpha (HADHA), was identified as a potential target. Immunohistochemical analyses revealed that HADHA tended to be overexpressed in a high-grade subtype of malignant lymphoma tissue. Clinicopathologic study revealed that HADHA overexpression was correlated with significantly worse overall survival (P= 0.013) and was an independent prognostic predictor in diffuse large B-cell lymphoma (P= 0.027). In vitro, downregulation of HADHA negatively regulated cell growth by causing G0/G1 arrest (P= 0.0008) similar to treatment with etomoxir, an inhibitor of FAO (P= 0.032). Moreover, downregulation of HADHA increased the susceptibility to doxorubicin (P= 0.002) and etoposide (P= 0.004). Moreover, these phenotypes were confirmed in an HADHA knockout system. Thus, we provide a basis for a novel therapeutic strategy through the regulation of HADHA and FAO in patients with refractory malignant lymphoma.</description><subject>13/106</subject><subject>13/109</subject><subject>13/31</subject><subject>13/51</subject><subject>631/67/1059/602</subject><subject>631/67/2327</subject><subject>82/58</subject><subject>Abnormalities</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>B-cell lymphoma</subject><subject>Cell death</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Correlation analysis</subject><subject>Down-Regulation</subject><subject>Doxorubicin</subject><subject>Drug Discovery</subject><subject>Enzymes</subject><subject>Etoposide</subject><subject>Fatty acids</subject><subject>Fatty Acids - metabolism</subject><subject>Female</subject><subject>Genetic abnormalities</subject><subject>Genetic transformation</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphoid tissue</subject><subject>Lymphoid Tissue - chemistry</subject><subject>Lymphoid Tissue - metabolism</subject><subject>Lymphoma</subject><subject>Lymphoma - metabolism</subject><subject>Lymphoma - mortality</subject><subject>Lymphoma - pathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondrial Trifunctional Protein, alpha Subunit - antagonists & inhibitors</subject><subject>Mitochondrial Trifunctional Protein, alpha Subunit - genetics</subject><subject>Mitochondrial Trifunctional Protein, alpha Subunit - metabolism</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Pathology</subject><subject>Phenotypes</subject><subject>Proteins</subject><subject>Proteome - analysis</subject><subject>Proteome - metabolism</subject><subject>Proteomics</subject><subject>Shotguns</subject><subject>Target recognition</subject><subject>Therapeutic applications</subject><subject>Tissues</subject><issn>0023-6837</issn><issn>1530-0307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><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>eNp9kc2KFDEURoMoTjv6AG4k4MZNaX4rKVw1o2MLA250HVLJrZ4MVakySQ_TPr1palRw0asQ7vm-XHIQek3Je0q4_pAF5Uo0hHYN4VQ37RO0oZKTeiPqKdoQwnjTaq4u0Iuc7wihQrTyObrgVDKlmd4gf21LOWLrgsc9FIvnh-BtCXPEEH8dJ8C77afdFoeMLY7zPYx4mQvEEuyIyy0ku8ChBIeLTXsoOEQ82THso40Fj8dpuZ0n-xI9G-yY4dXjeYl-XH_-frVrbr59-Xq1vWmc6GRptPMgW6pkp1qltLCEc-lVD30riQSiFRsIr1NBPWnZIPUAA2feUS4F7TW_RO_W3iXNPw-Qi5lCdjCONsJ8yIaxjnVaKckq-vY_9G4-pFi3M0wo0WlKKD9L8VZS2RF-6qIr5dKcc4LBLClMNh0NJeYkyqyiTBVlTqJMWzNvHpsP_QT-b-KPmQqwFch1FPeQ_j19rvXjGoL6y_ehhrILEB34kMAV4-dwJv0bqB-unQ</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Yamamoto, Kouhei</creator><creator>Abe, Shinya</creator><creator>Honda, Ayaka</creator><creator>Hashimoto, Jun</creator><creator>Aizawa, Yuuki</creator><creator>Ishibashi, Sachiko</creator><creator>Takemura, Taro</creator><creator>Hanagata, Nobutaka</creator><creator>Yamamoto, Masahide</creator><creator>Miura, Osamu</creator><creator>Kurata, Morito</creator><creator>Kitagawa, Masanobu</creator><general>Elsevier Inc</general><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</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>C1K</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20200301</creationdate><title>Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma</title><author>Yamamoto, Kouhei ; Abe, Shinya ; Honda, Ayaka ; Hashimoto, Jun ; Aizawa, Yuuki ; Ishibashi, Sachiko ; Takemura, Taro ; Hanagata, Nobutaka ; Yamamoto, Masahide ; Miura, Osamu ; Kurata, Morito ; Kitagawa, Masanobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-8cde561759767784a0335d7beb6505e0872f0359741d062f58fef32dc13541b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/106</topic><topic>13/109</topic><topic>13/31</topic><topic>13/51</topic><topic>631/67/1059/602</topic><topic>631/67/2327</topic><topic>82/58</topic><topic>Abnormalities</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>B-cell lymphoma</topic><topic>Cell death</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Correlation analysis</topic><topic>Down-Regulation</topic><topic>Doxorubicin</topic><topic>Drug Discovery</topic><topic>Enzymes</topic><topic>Etoposide</topic><topic>Fatty acids</topic><topic>Fatty Acids - metabolism</topic><topic>Female</topic><topic>Genetic abnormalities</topic><topic>Genetic transformation</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphoid tissue</topic><topic>Lymphoid Tissue - chemistry</topic><topic>Lymphoid Tissue - metabolism</topic><topic>Lymphoma</topic><topic>Lymphoma - metabolism</topic><topic>Lymphoma - mortality</topic><topic>Lymphoma - pathology</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>Mitochondrial Trifunctional Protein, alpha Subunit - antagonists & inhibitors</topic><topic>Mitochondrial Trifunctional Protein, alpha Subunit - genetics</topic><topic>Mitochondrial Trifunctional Protein, alpha Subunit - metabolism</topic><topic>Oxidation</topic><topic>Oxidation-Reduction</topic><topic>Pathology</topic><topic>Phenotypes</topic><topic>Proteins</topic><topic>Proteome - analysis</topic><topic>Proteome - metabolism</topic><topic>Proteomics</topic><topic>Shotguns</topic><topic>Target recognition</topic><topic>Therapeutic applications</topic><topic>Tissues</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamamoto, Kouhei</creatorcontrib><creatorcontrib>Abe, Shinya</creatorcontrib><creatorcontrib>Honda, Ayaka</creatorcontrib><creatorcontrib>Hashimoto, Jun</creatorcontrib><creatorcontrib>Aizawa, Yuuki</creatorcontrib><creatorcontrib>Ishibashi, Sachiko</creatorcontrib><creatorcontrib>Takemura, Taro</creatorcontrib><creatorcontrib>Hanagata, Nobutaka</creatorcontrib><creatorcontrib>Yamamoto, Masahide</creatorcontrib><creatorcontrib>Miura, Osamu</creatorcontrib><creatorcontrib>Kurata, Morito</creatorcontrib><creatorcontrib>Kitagawa, Masanobu</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</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 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>Environmental Sciences and Pollution Management</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>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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</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>MEDLINE - Academic</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamamoto, Kouhei</au><au>Abe, Shinya</au><au>Honda, Ayaka</au><au>Hashimoto, Jun</au><au>Aizawa, Yuuki</au><au>Ishibashi, Sachiko</au><au>Takemura, Taro</au><au>Hanagata, Nobutaka</au><au>Yamamoto, Masahide</au><au>Miura, Osamu</au><au>Kurata, Morito</au><au>Kitagawa, Masanobu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>100</volume><issue>3</issue><spage>353</spage><epage>362</epage><pages>353-362</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>Cancer cells, including malignant lymphoma cells, alter their metabolism, termed “metabolic reprograming,” on initiation of malignant transformation as well as upon accumulation of genetic abnormalities. Here, to identify a novel therapeutic target involved in the metabolic changes during malignant lymphoma, we performed global analyses combined with shotgun proteomics, in silico database analysis, and clinic-pathologic analysis of nonneoplastic lymphoid tissue and malignant lymphoma tissue and verified the molecular functions in vitro. In total, 2002 proteins were detected from both samples and proteins related to fatty acid beta-oxidation (FAO) were detected more frequently in malignant lymphoma tissue. Consequently, the most frequently detected protein, the mitochondrial trifunctional enzyme subunit-alpha (HADHA), was identified as a potential target. Immunohistochemical analyses revealed that HADHA tended to be overexpressed in a high-grade subtype of malignant lymphoma tissue. Clinicopathologic study revealed that HADHA overexpression was correlated with significantly worse overall survival (P= 0.013) and was an independent prognostic predictor in diffuse large B-cell lymphoma (P= 0.027). In vitro, downregulation of HADHA negatively regulated cell growth by causing G0/G1 arrest (P= 0.0008) similar to treatment with etomoxir, an inhibitor of FAO (P= 0.032). Moreover, downregulation of HADHA increased the susceptibility to doxorubicin (P= 0.002) and etoposide (P= 0.004). Moreover, these phenotypes were confirmed in an HADHA knockout system. Thus, we provide a basis for a novel therapeutic strategy through the regulation of HADHA and FAO in patients with refractory malignant lymphoma.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>31527828</pmid><doi>10.1038/s41374-019-0318-6</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/106 13/109 13/31 13/51 631/67/1059/602 631/67/2327 82/58 Abnormalities Antineoplastic Agents - pharmacology B-cell lymphoma Cell death Cell growth Cell Line, Tumor Cell Survival - drug effects Correlation analysis Down-Regulation Doxorubicin Drug Discovery Enzymes Etoposide Fatty acids Fatty Acids - metabolism Female Genetic abnormalities Genetic transformation Humans Laboratory Medicine Lymphocytes Lymphocytes B Lymphoid tissue Lymphoid Tissue - chemistry Lymphoid Tissue - metabolism Lymphoma Lymphoma - metabolism Lymphoma - mortality Lymphoma - pathology Male Medicine Medicine & Public Health Metabolic pathways Metabolism Middle Aged Mitochondria Mitochondrial Trifunctional Protein, alpha Subunit - antagonists & inhibitors Mitochondrial Trifunctional Protein, alpha Subunit - genetics Mitochondrial Trifunctional Protein, alpha Subunit - metabolism Oxidation Oxidation-Reduction Pathology Phenotypes Proteins Proteome - analysis Proteome - metabolism Proteomics Shotguns Target recognition Therapeutic applications Tissues |
| title | Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma |
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