FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer
Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p...
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| Veröffentlicht in: | Cell death & disease 2020-10, Vol.11 (10), p.839, Article 839 |
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| creator | Qiu, Li Hu, Linfei Wang, Huijuan Li, Jinling Ruan, Xianhui Sun, Bingsheng Zhi, Jingtai Zheng, Xiangqian Gu, Lin Gao, Ming Kong, Pengzhou Zhang, Jun |
| description | Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERβ and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression. |
| doi_str_mv | 10.1038/s41419-020-03052-1 |
| format | Article |
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Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERβ and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-020-03052-1</identifier><identifier>PMID: 33037185</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/35 ; 38/109 ; 38/77 ; 38/89 ; 38/90 ; 59/5 ; 631/80/39/2346 ; 631/80/82/23 ; 64/60 ; 82/51 ; 96/2 ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cell Biology ; Cell Culture ; Cell Cycle - genetics ; Cell Proliferation - genetics ; Estrogen Receptor beta - genetics ; Genes, Tumor Suppressor - physiology ; Humans ; Immunology ; Life Sciences ; Lung Neoplasms - genetics ; RNA, Messenger - metabolism</subject><ispartof>Cell death & disease, 2020-10, Vol.11 (10), p.839, Article 839</ispartof><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-1cdcb87a7095177c7fe22da55f1a396cbecd2fde709e604004964cf1f05aa5e43</citedby><cites>FETCH-LOGICAL-c446t-1cdcb87a7095177c7fe22da55f1a396cbecd2fde709e604004964cf1f05aa5e43</cites><orcidid>0000-0002-2743-2247</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/PMC7547721/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547721/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33037185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiu, Li</creatorcontrib><creatorcontrib>Hu, Linfei</creatorcontrib><creatorcontrib>Wang, Huijuan</creatorcontrib><creatorcontrib>Li, Jinling</creatorcontrib><creatorcontrib>Ruan, Xianhui</creatorcontrib><creatorcontrib>Sun, Bingsheng</creatorcontrib><creatorcontrib>Zhi, Jingtai</creatorcontrib><creatorcontrib>Zheng, Xiangqian</creatorcontrib><creatorcontrib>Gu, Lin</creatorcontrib><creatorcontrib>Gao, Ming</creatorcontrib><creatorcontrib>Kong, Pengzhou</creatorcontrib><creatorcontrib>Zhang, Jun</creatorcontrib><title>FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERβ and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.</description><subject>14/35</subject><subject>38/109</subject><subject>38/77</subject><subject>38/89</subject><subject>38/90</subject><subject>59/5</subject><subject>631/80/39/2346</subject><subject>631/80/82/23</subject><subject>64/60</subject><subject>82/51</subject><subject>96/2</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Cycle - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Estrogen Receptor beta - genetics</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>Lung Neoplasms - genetics</subject><subject>RNA, Messenger - metabolism</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>EIF</sourceid><recordid>eNp9kdFqHSEQhqU0NCHJC-Si-AK26uq6e1MIp0lbCATa5Fpcnd0YXF10T-FAnqoP0meqp6cN6U3nZgb--T9lfoQuGH3HaNO9L4IJ1hPKKaENlZywV-iEU8GI6Lr-9Yv5GJ2X8khrNQ3lsn2DjuvQKNbJE_R0fXn3DWeYtsGsUPCSws7MPgIefCq7uD5A8QUPO7zkNKfVxwnfftxgB1M2zqw-RewjNhFfff35gzhYIDqIK55NjJD3WkyRlNmEQCyEgMO2IqyJFvIZOhpNKHD-p5-i--uru81ncnP76cvm8oZYIdqVMOvs0CmjaC-ZUlaNwLkzUo7MNH1rB7COjw6qDi0VlIq-FXZkI5XGSBDNKfpw4C7bYQZn6_-yCXrJfjZ5p5Px-l8l-gc9pe9aSaEUZxXADwCbUykZxmcvo3ofhz7EoWsc-nccem96-_LVZ8vf49eF5rBQqhQnyPoxbXOsl_gf9hfj3Jmd</recordid><startdate>20201009</startdate><enddate>20201009</enddate><creator>Qiu, Li</creator><creator>Hu, Linfei</creator><creator>Wang, Huijuan</creator><creator>Li, Jinling</creator><creator>Ruan, Xianhui</creator><creator>Sun, Bingsheng</creator><creator>Zhi, Jingtai</creator><creator>Zheng, Xiangqian</creator><creator>Gu, Lin</creator><creator>Gao, Ming</creator><creator>Kong, Pengzhou</creator><creator>Zhang, Jun</creator><general>Nature Publishing Group UK</general><scope>C6C</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>5PM</scope><orcidid>https://orcid.org/0000-0002-2743-2247</orcidid></search><sort><creationdate>20201009</creationdate><title>FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer</title><author>Qiu, Li ; Hu, Linfei ; Wang, Huijuan ; Li, Jinling ; Ruan, Xianhui ; Sun, Bingsheng ; Zhi, Jingtai ; Zheng, Xiangqian ; Gu, Lin ; Gao, Ming ; Kong, Pengzhou ; Zhang, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-1cdcb87a7095177c7fe22da55f1a396cbecd2fde709e604004964cf1f05aa5e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>14/35</topic><topic>38/109</topic><topic>38/77</topic><topic>38/89</topic><topic>38/90</topic><topic>59/5</topic><topic>631/80/39/2346</topic><topic>631/80/82/23</topic><topic>64/60</topic><topic>82/51</topic><topic>96/2</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Cycle - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Estrogen Receptor beta - genetics</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Life Sciences</topic><topic>Lung Neoplasms - genetics</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiu, Li</creatorcontrib><creatorcontrib>Hu, Linfei</creatorcontrib><creatorcontrib>Wang, Huijuan</creatorcontrib><creatorcontrib>Li, Jinling</creatorcontrib><creatorcontrib>Ruan, Xianhui</creatorcontrib><creatorcontrib>Sun, Bingsheng</creatorcontrib><creatorcontrib>Zhi, Jingtai</creatorcontrib><creatorcontrib>Zheng, Xiangqian</creatorcontrib><creatorcontrib>Gu, Lin</creatorcontrib><creatorcontrib>Gao, Ming</creatorcontrib><creatorcontrib>Kong, Pengzhou</creatorcontrib><creatorcontrib>Zhang, Jun</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Qiu, Li</au><au>Hu, Linfei</au><au>Wang, Huijuan</au><au>Li, Jinling</au><au>Ruan, Xianhui</au><au>Sun, Bingsheng</au><au>Zhi, Jingtai</au><au>Zheng, Xiangqian</au><au>Gu, Lin</au><au>Gao, Ming</au><au>Kong, Pengzhou</au><au>Zhang, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2020-10-09</date><risdate>2020</risdate><volume>11</volume><issue>10</issue><spage>839</spage><pages>839-</pages><artnum>839</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERβ and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33037185</pmid><doi>10.1038/s41419-020-03052-1</doi><orcidid>https://orcid.org/0000-0002-2743-2247</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 14/35 38/109 38/77 38/89 38/90 59/5 631/80/39/2346 631/80/82/23 64/60 82/51 96/2 Antibodies Biochemistry Biomedical and Life Sciences Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Cell Biology Cell Culture Cell Cycle - genetics Cell Proliferation - genetics Estrogen Receptor beta - genetics Genes, Tumor Suppressor - physiology Humans Immunology Life Sciences Lung Neoplasms - genetics RNA, Messenger - metabolism |
| title | FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer |
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