Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence
REV-ERBs, nuclear hormone receptors that regulate transcription as part of the circadian clock cell machinery, inhibit autophagy and lipogenesis in premalignant and malignant cells and impair tumour growth in vivo . Tumours restrained by REV-ERBs The circadian clock regulates many of the physiologic...
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| Published in | Nature (London) Vol. 553; no. 7688; pp. 351 - 355 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
18.01.2018
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | REV-ERBs, nuclear hormone receptors that regulate transcription as part of the circadian clock cell machinery, inhibit autophagy and lipogenesis in premalignant and malignant cells and impair tumour growth
in vivo
.
Tumours restrained by REV-ERBs
The circadian clock regulates many of the physiological functions of an organism. Additionally, links between the circadian clock machinery and cancer have been demonstrated. Gabriele Sulli
et al
. have explored this link further by unravelling the functions of REV-ERBs. These nuclear hormone receptors regulate transcription and are an essential component of the circadian clock. Treatment of cancer cells with REV-ERB agonists results in cell death, through inhibition of autophagy and
de novo
lipogenesis. The agonists also impaired tumour growth
in vivo
.
The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response
1
,
2
. Perturbations of these processes are hallmarks of cancer
3
and chronic circadian rhythm disruption predisposes individuals to tumour development
1
,
4
. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock
5
,
6
. Here we show that two agonists of REV-ERBs—SR9009 and SR9011—are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and
de novo
lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth
in vivo
and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and
de novo
lipogenesis, with selective activity towards malignant and benign neoplasms. |
|---|---|
| AbstractList | REV-ERBs, nuclear hormone receptors that regulate transcription as part of the circadian clock cell machinery, inhibit autophagy and lipogenesis in premalignant and malignant cells and impair tumour growth in vivo. The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response 1 , 2 . Perturbations of these processes are hallmarks of cancer 3 and chronic circadian rhythm disruption predisposes to tumor development 1 , 4 . This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combatting cancer. The nuclear hormone receptors REV-ERBα and REV-ERBβ (REV-ERBs) are essential components of the circadian clock 5 , 6 . Here we show that SR9009 and SR9011, two different agonists of REV-ERBs are specifically lethal to cancer cells and oncogene-induced senescent (OIS) cells, including melanocytic naevi, while having no effect on viability of normal cells or tissues. Anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as H-RAS, BRAF, PIK3CA, and others), and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 plays a critical role in evoking an apoptotic response in malignant cells. Importantly, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing any overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective novel antitumor strategy, identifying the existence of a previously unknown class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are novel autophagy and de novo lipogenesis inhibitors with selective activity towards malignant and benign neoplasms. REV-ERBs, nuclear hormone receptors that regulate transcription as part of the circadian clock cell machinery, inhibit autophagy and lipogenesis in premalignant and malignant cells and impair tumour growth in vivo . Tumours restrained by REV-ERBs The circadian clock regulates many of the physiological functions of an organism. Additionally, links between the circadian clock machinery and cancer have been demonstrated. Gabriele Sulli et al . have explored this link further by unravelling the functions of REV-ERBs. These nuclear hormone receptors regulate transcription and are an essential component of the circadian clock. Treatment of cancer cells with REV-ERB agonists results in cell death, through inhibition of autophagy and de novo lipogenesis. The agonists also impaired tumour growth in vivo . The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response 1 , 2 . Perturbations of these processes are hallmarks of cancer 3 and chronic circadian rhythm disruption predisposes individuals to tumour development 1 , 4 . This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock 5 , 6 . Here we show that two agonists of REV-ERBs—SR9009 and SR9011—are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms. The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBa (also known as NR1D1) and REV-ERBß (also known as NR1D2), are essential components of the circadian clock. Here we show that two agonists of REVERBs-SR9009 and SR9011 -are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms. The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock. Here we show that two agonists of REV-ERBs-SR9009 and SR9011-are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms.The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock. Here we show that two agonists of REV-ERBs-SR9009 and SR9011-are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms. The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock. Here we show that two agonists of REV-ERBs-SR9009 and SR9011-are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms. |
| Audience | Academic |
| Author | Verma, Inder M. Panda, Satchidananda Saghatelian, Alan Kolar, Matthew J. Puca, Francesca Sulli, Gabriele Rommel, Amy Wang, Xiaojie Plikus, Maksim V. |
| AuthorAffiliation | 5 Department of Genomic Medicine, The University of Texas MD, Anderson Cancer Center, Houston, TX 77030, USA 4 Clayton Foundation Laboratories of Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA 2 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA 1 Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA 3 Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA |
| AuthorAffiliation_xml | – name: 2 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA – name: 5 Department of Genomic Medicine, The University of Texas MD, Anderson Cancer Center, Houston, TX 77030, USA – name: 3 Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA – name: 1 Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA – name: 4 Clayton Foundation Laboratories of Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA |
| Author_xml | – sequence: 1 givenname: Gabriele surname: Sulli fullname: Sulli, Gabriele email: gsulli@salk.edu organization: Regulatory Biology Laboratory, Salk Institute for Biological Studies – sequence: 2 givenname: Amy surname: Rommel fullname: Rommel, Amy organization: Laboratory of Genetics, Salk Institute for Biological Studies – sequence: 3 givenname: Xiaojie surname: Wang fullname: Wang, Xiaojie organization: Department of Developmental and Cell Biology, University of California, Irvine – sequence: 4 givenname: Matthew J. surname: Kolar fullname: Kolar, Matthew J. organization: Clayton Foundation Laboratories of Peptide Biology, Salk Institute for Biological Studies – sequence: 5 givenname: Francesca surname: Puca fullname: Puca, Francesca organization: Department of Genomic Medicine, The University of Texas MD, Anderson Cancer Center – sequence: 6 givenname: Alan surname: Saghatelian fullname: Saghatelian, Alan organization: Clayton Foundation Laboratories of Peptide Biology, Salk Institute for Biological Studies – sequence: 7 givenname: Maksim V. surname: Plikus fullname: Plikus, Maksim V. organization: Department of Developmental and Cell Biology, University of California, Irvine – sequence: 8 givenname: Inder M. surname: Verma fullname: Verma, Inder M. organization: Laboratory of Genetics, Salk Institute for Biological Studies – sequence: 9 givenname: Satchidananda surname: Panda fullname: Panda, Satchidananda email: satchin@salk.edu organization: Regulatory Biology Laboratory, Salk Institute for Biological Studies |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29320480$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1139/y59-099 10.1021/bi0480335 10.1038/ncb2170 10.1016/S0092-8674(00)81902-9 10.1038/nrd.2017.116 10.18632/aging.100323 10.1038/nri3386 10.1038/nm.4010 10.1038/nm.1863 10.1038/nrc1072 10.1038/nm.3213 10.1126/science.1150179 10.1038/nrd4002 10.1038/nrc3262 10.1101/gad.186858.112 10.1016/S1470-2045(07)70373-X 10.1101/gad.519709 10.4161/cc.19800 10.1016/j.cell.2013.09.034 10.1016/S0092-8674(02)00825-5 10.1126/science.1243417 10.1038/nature03890 10.1016/j.cmet.2013.05.017 10.1186/gb-2008-9-9-r137 10.1038/nrm2233 10.1038/nature12209 10.1002/stem.2053 10.1210/en.2011-1595 10.1038/nature11048 10.1038/nature11704 10.1038/emboj.2011.322 10.1016/j.cell.2011.02.013 10.1038/nm.4181 10.1038/nature11030 10.1016/S0092-8674(02)00961-3 10.1016/j.febslet.2010.03.017 10.1073/pnas.1215935110 10.1038/nrd3802 10.1038/nature07385 |
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| References | Zhang (CR35) 2008; 9 Yu, Weaver (CR7) 2011; 3 Solt (CR14) 2012; 485 Marumoto (CR32) 2009; 15 Fu, Pelicano, Liu, Huang, Lee (CR9) 2002; 111 Sancar (CR10) 2010; 584 Bugge (CR6) 2012; 26 Straif (CR4) 2007; 8 Lam (CR36) 2013; 498 Svensson (CR39) 2016; 22 CR31 Fu, Lee (CR1) 2003; 3 Currie, Schulze, Zechner, Walther, Farese (CR19) 2013; 18 White (CR20) 2012; 12 Serrano, Lin, McCurrach, Beach, Lowe (CR23) 1997; 88 Woldt (CR15) 2013; 19 Ma, Panda, Lin (CR22) 2011; 30 Chang (CR29) 2016; 22 Hossain (CR34) 2015; 33 Young (CR27) 2009; 23 Hanahan, Weinberg (CR3) 2011; 144 Saghatelian (CR38) 2004; 43 Di Micco (CR33) 2011; 13 Bass (CR11) 2012; 491 Yin (CR13) 2007; 318 Scheiermann, Kunisaki, Frenette (CR2) 2013; 13 Michaloglou (CR28) 2005; 436 Cho (CR5) 2012; 485 Brennan (CR30) 2013; 155 Childs (CR25) 2017; 16 Peek (CR18) 2013; 342 Quijano (CR26) 2012; 11 Vieira (CR16) 2012; 153 Bligh, Dyer (CR37) 1959; 37 Plikus (CR8) 2013; 110 Gorrini, Harris, Mak (CR17) 2013; 12 Preitner (CR12) 2002; 110 Rubinsztein, Codogno, Levine (CR21) 2012; 11 Campisi, d’Adda di Fagagna (CR24) 2007; 8 L Fu (BFnature25170_CR1) 2003; 3 C Scheiermann (BFnature25170_CR2) 2013; 13 A Hossain (BFnature25170_CR34) 2015; 33 D Hanahan (BFnature25170_CR3) 2011; 144 E Woldt (BFnature25170_CR15) 2013; 19 EG Bligh (BFnature25170_CR37) 1959; 37 C Quijano (BFnature25170_CR26) 2012; 11 CW Brennan (BFnature25170_CR30) 2013; 155 T Marumoto (BFnature25170_CR32) 2009; 15 C Gorrini (BFnature25170_CR17) 2013; 12 A Sancar (BFnature25170_CR10) 2010; 584 EA Yu (BFnature25170_CR7) 2011; 3 E White (BFnature25170_CR20) 2012; 12 MV Plikus (BFnature25170_CR8) 2013; 110 J Campisi (BFnature25170_CR24) 2007; 8 CB Peek (BFnature25170_CR18) 2013; 342 H Cho (BFnature25170_CR5) 2012; 485 L Yin (BFnature25170_CR13) 2007; 318 LA Solt (BFnature25170_CR14) 2012; 485 RU Svensson (BFnature25170_CR39) 2016; 22 E Vieira (BFnature25170_CR16) 2012; 153 MT Lam (BFnature25170_CR36) 2013; 498 K Straif (BFnature25170_CR4) 2007; 8 E Currie (BFnature25170_CR19) 2013; 18 D Ma (BFnature25170_CR22) 2011; 30 Y Zhang (BFnature25170_CR35) 2008; 9 N Preitner (BFnature25170_CR12) 2002; 110 A Bugge (BFnature25170_CR6) 2012; 26 J Bass (BFnature25170_CR11) 2012; 491 DC Rubinsztein (BFnature25170_CR21) 2012; 11 AR Young (BFnature25170_CR27) 2009; 23 BG Childs (BFnature25170_CR25) 2017; 16 A Saghatelian (BFnature25170_CR38) 2004; 43 M Serrano (BFnature25170_CR23) 1997; 88 C Michaloglou (BFnature25170_CR28) 2005; 436 L Fu (BFnature25170_CR9) 2002; 111 BFnature25170_CR31 J Chang (BFnature25170_CR29) 2016; 22 R Di Micco (BFnature25170_CR33) 2011; 13 29666473 - Cell Death Differ. 2018 Jun;25(6):1005-1006. doi: 10.1038/s41418-018-0102-y. 29352049 - Cancer Discov. 2018 Mar;8(3):261. doi: 10.1158/2159-8290.CD-RW2018-011. |
| References_xml | – volume: 37 start-page: 911 year: 1959 end-page: 917 ident: CR37 article-title: A rapid method of total lipid extraction and purification publication-title: Can. J. Biochem. Physiol. doi: 10.1139/y59-099 – volume: 43 start-page: 14332 year: 2004 end-page: 14339 ident: CR38 article-title: Assignment of endogenous substrates to enzymes by global metabolite profiling publication-title: Biochemistry doi: 10.1021/bi0480335 – volume: 13 start-page: 292 year: 2011 end-page: 302 ident: CR33 article-title: Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer publication-title: Nat. Cell Biol. doi: 10.1038/ncb2170 – volume: 88 start-page: 593 year: 1997 end-page: 602 ident: CR23 article-title: Oncogenic provokes premature cell senescence associated with accumulation of p53 and p16 publication-title: Cell doi: 10.1016/S0092-8674(00)81902-9 – volume: 16 start-page: 718 year: 2017 end-page: 735 ident: CR25 article-title: Senescent cells: an emerging target for diseases of ageing publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd.2017.116 – volume: 3 start-page: 479 year: 2011 end-page: 493 ident: CR7 article-title: Disrupting the circadian clock: gene-specific effects on aging, cancer, and other phenotypes publication-title: Aging doi: 10.18632/aging.100323 – volume: 13 start-page: 190 year: 2013 end-page: 198 ident: CR2 article-title: Circadian control of the immune system publication-title: Nat. Rev. Immunol. doi: 10.1038/nri3386 – volume: 22 start-page: 78 year: 2016 end-page: 83 ident: CR29 article-title: Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice publication-title: Nat. Med. doi: 10.1038/nm.4010 – volume: 15 start-page: 110 year: 2009 end-page: 116 ident: CR32 article-title: Development of a novel mouse glioma model using lentiviral vectors publication-title: Nat. Med. doi: 10.1038/nm.1863 – volume: 3 start-page: 350 year: 2003 end-page: 361 ident: CR1 article-title: The circadian clock: pacemaker and tumour suppressor publication-title: Nat. Rev. Cancer doi: 10.1038/nrc1072 – volume: 19 start-page: 1039 year: 2013 end-page: 1046 ident: CR15 article-title: REV-ERB-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy publication-title: Nat. Med. doi: 10.1038/nm.3213 – volume: 318 start-page: 1786 year: 2007 end-page: 1789 ident: CR13 article-title: REV-ERBα, a heme sensor that coordinates metabolic and circadian pathways publication-title: Science doi: 10.1126/science.1150179 – volume: 12 start-page: 931 year: 2013 end-page: 947 ident: CR17 article-title: Modulation of oxidative stress as an anticancer strategy publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd4002 – volume: 12 start-page: 401 year: 2012 end-page: 410 ident: CR20 article-title: Deconvoluting the context-dependent role for autophagy in cancer publication-title: Nat. Rev. Cancer doi: 10.1038/nrc3262 – volume: 26 start-page: 657 year: 2012 end-page: 667 ident: CR6 article-title: REV-ERBα and REV-ERBβ coordinately protect the circadian clock and normal metabolic function publication-title: Genes Dev. doi: 10.1101/gad.186858.112 – volume: 8 start-page: 1065 year: 2007 end-page: 1066 ident: CR4 article-title: Carcinogenicity of shift-work, painting, and fire-fighting publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(07)70373-X – volume: 23 start-page: 798 year: 2009 end-page: 803 ident: CR27 article-title: Autophagy mediates the mitotic senescence transition publication-title: Genes Dev. doi: 10.1101/gad.519709 – volume: 11 start-page: 1383 year: 2012 end-page: 1392 ident: CR26 article-title: Oncogene-induced senescence results in marked metabolic and bioenergetic alterations publication-title: Cell Cycle doi: 10.4161/cc.19800 – volume: 155 start-page: 462 year: 2013 end-page: 477 ident: CR30 article-title: The somatic genomic landscape of glioblastoma publication-title: Cell doi: 10.1016/j.cell.2013.09.034 – volume: 110 start-page: 251 year: 2002 end-page: 260 ident: CR12 article-title: The orphan nuclear receptor REV-ERBα controls circadian transcription within the positive limb of the mammalian circadian oscillator publication-title: Cell doi: 10.1016/S0092-8674(02)00825-5 – volume: 342 start-page: 1243417 year: 2013 ident: CR18 article-title: Circadian clock NAD cycle drives mitochondrial oxidative metabolism in mice publication-title: Science doi: 10.1126/science.1243417 – volume: 436 start-page: 720 year: 2005 end-page: 724 ident: CR28 article-title: BRAF -associated senescence-like cell cycle arrest of human naevi publication-title: Nature doi: 10.1038/nature03890 – volume: 18 start-page: 153 year: 2013 end-page: 161 ident: CR19 article-title: Cellular fatty acid metabolism and cancer publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.05.017 – volume: 9 start-page: R137 year: 2008 ident: CR35 article-title: Model-based analysis of ChIP–seq (MACS) publication-title: Genome Biol. doi: 10.1186/gb-2008-9-9-r137 – volume: 8 start-page: 729 year: 2007 end-page: 740 ident: CR24 article-title: Cellular senescence: when bad things happen to good cells publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2233 – volume: 498 start-page: 511 year: 2013 end-page: 515 ident: CR36 article-title: Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription publication-title: Nature doi: 10.1038/nature12209 – ident: CR31 – volume: 33 start-page: 2400 year: 2015 end-page: 2415 ident: CR34 article-title: Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway publication-title: Stem Cells doi: 10.1002/stem.2053 – volume: 153 start-page: 592 year: 2012 end-page: 601 ident: CR16 article-title: The clock gene α regulates pancreatic β-cell function: modulation by leptin and high-fat diet publication-title: Endocrinology doi: 10.1210/en.2011-1595 – volume: 485 start-page: 123 year: 2012 end-page: 127 ident: CR5 article-title: Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β publication-title: Nature doi: 10.1038/nature11048 – volume: 491 start-page: 348 year: 2012 end-page: 356 ident: CR11 article-title: Circadian topology of metabolism publication-title: Nature doi: 10.1038/nature11704 – volume: 30 start-page: 4642 year: 2011 end-page: 4651 ident: CR22 article-title: Temporal orchestration of circadian autophagy rhythm by C/EBPβ publication-title: EMBO J. doi: 10.1038/emboj.2011.322 – volume: 144 start-page: 646 year: 2011 end-page: 674 ident: CR3 article-title: Hallmarks of cancer: the next generation publication-title: Cell doi: 10.1016/j.cell.2011.02.013 – volume: 22 start-page: 1108 year: 2016 end-page: 1119 ident: CR39 article-title: Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models publication-title: Nat. Med. doi: 10.1038/nm.4181 – volume: 485 start-page: 62 year: 2012 end-page: 68 ident: CR14 article-title: Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists publication-title: Nature doi: 10.1038/nature11030 – volume: 111 start-page: 41 year: 2002 end-page: 50 ident: CR9 article-title: The circadian gene plays an important role in tumor suppression and DNA damage response publication-title: Cell doi: 10.1016/S0092-8674(02)00961-3 – volume: 584 start-page: 2618 year: 2010 end-page: 2625 ident: CR10 article-title: Circadian clock control of the cellular response to DNA damage publication-title: FEBS Lett. doi: 10.1016/j.febslet.2010.03.017 – volume: 110 start-page: E2106 year: 2013 end-page: E2115 ident: CR8 article-title: Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1215935110 – volume: 11 start-page: 709 year: 2012 end-page: 730 ident: CR21 article-title: Autophagy modulation as a potential therapeutic target for diverse diseases publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd3802 – volume: 144 start-page: 646 year: 2011 ident: BFnature25170_CR3 publication-title: Cell doi: 10.1016/j.cell.2011.02.013 – volume: 8 start-page: 729 year: 2007 ident: BFnature25170_CR24 publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2233 – volume: 26 start-page: 657 year: 2012 ident: BFnature25170_CR6 publication-title: Genes Dev. doi: 10.1101/gad.186858.112 – volume: 13 start-page: 190 year: 2013 ident: BFnature25170_CR2 publication-title: Nat. Rev. Immunol. doi: 10.1038/nri3386 – volume: 12 start-page: 931 year: 2013 ident: BFnature25170_CR17 publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd4002 – volume: 33 start-page: 2400 year: 2015 ident: BFnature25170_CR34 publication-title: Stem Cells doi: 10.1002/stem.2053 – volume: 15 start-page: 110 year: 2009 ident: BFnature25170_CR32 publication-title: Nat. Med. doi: 10.1038/nm.1863 – ident: BFnature25170_CR31 doi: 10.1038/nature07385 – volume: 22 start-page: 78 year: 2016 ident: BFnature25170_CR29 publication-title: Nat. Med. doi: 10.1038/nm.4010 – volume: 8 start-page: 1065 year: 2007 ident: BFnature25170_CR4 publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(07)70373-X – volume: 13 start-page: 292 year: 2011 ident: BFnature25170_CR33 publication-title: Nat. Cell Biol. doi: 10.1038/ncb2170 – volume: 18 start-page: 153 year: 2013 ident: BFnature25170_CR19 publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.05.017 – volume: 3 start-page: 350 year: 2003 ident: BFnature25170_CR1 publication-title: Nat. Rev. Cancer doi: 10.1038/nrc1072 – volume: 110 start-page: E2106 year: 2013 ident: BFnature25170_CR8 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1215935110 – volume: 16 start-page: 718 year: 2017 ident: BFnature25170_CR25 publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd.2017.116 – volume: 318 start-page: 1786 year: 2007 ident: BFnature25170_CR13 publication-title: Science doi: 10.1126/science.1150179 – volume: 23 start-page: 798 year: 2009 ident: BFnature25170_CR27 publication-title: Genes Dev. doi: 10.1101/gad.519709 – volume: 3 start-page: 479 year: 2011 ident: BFnature25170_CR7 publication-title: Aging doi: 10.18632/aging.100323 – volume: 155 start-page: 462 year: 2013 ident: BFnature25170_CR30 publication-title: Cell doi: 10.1016/j.cell.2013.09.034 – volume: 485 start-page: 62 year: 2012 ident: BFnature25170_CR14 publication-title: Nature doi: 10.1038/nature11030 – volume: 584 start-page: 2618 year: 2010 ident: BFnature25170_CR10 publication-title: FEBS Lett. doi: 10.1016/j.febslet.2010.03.017 – volume: 19 start-page: 1039 year: 2013 ident: BFnature25170_CR15 publication-title: Nat. Med. doi: 10.1038/nm.3213 – volume: 153 start-page: 592 year: 2012 ident: BFnature25170_CR16 publication-title: Endocrinology doi: 10.1210/en.2011-1595 – volume: 43 start-page: 14332 year: 2004 ident: BFnature25170_CR38 publication-title: Biochemistry doi: 10.1021/bi0480335 – volume: 11 start-page: 709 year: 2012 ident: BFnature25170_CR21 publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd3802 – volume: 88 start-page: 593 year: 1997 ident: BFnature25170_CR23 publication-title: Cell doi: 10.1016/S0092-8674(00)81902-9 – volume: 12 start-page: 401 year: 2012 ident: BFnature25170_CR20 publication-title: Nat. Rev. Cancer doi: 10.1038/nrc3262 – volume: 37 start-page: 911 year: 1959 ident: BFnature25170_CR37 publication-title: Can. J. Biochem. Physiol. doi: 10.1139/y59-099 – volume: 30 start-page: 4642 year: 2011 ident: BFnature25170_CR22 publication-title: EMBO J. doi: 10.1038/emboj.2011.322 – volume: 22 start-page: 1108 year: 2016 ident: BFnature25170_CR39 publication-title: Nat. Med. doi: 10.1038/nm.4181 – volume: 485 start-page: 123 year: 2012 ident: BFnature25170_CR5 publication-title: Nature doi: 10.1038/nature11048 – volume: 436 start-page: 720 year: 2005 ident: BFnature25170_CR28 publication-title: Nature doi: 10.1038/nature03890 – volume: 491 start-page: 348 year: 2012 ident: BFnature25170_CR11 publication-title: Nature doi: 10.1038/nature11704 – volume: 11 start-page: 1383 year: 2012 ident: BFnature25170_CR26 publication-title: Cell Cycle doi: 10.4161/cc.19800 – volume: 9 start-page: R137 year: 2008 ident: BFnature25170_CR35 publication-title: Genome Biol. doi: 10.1186/gb-2008-9-9-r137 – volume: 111 start-page: 41 year: 2002 ident: BFnature25170_CR9 publication-title: Cell doi: 10.1016/S0092-8674(02)00961-3 – volume: 498 start-page: 511 year: 2013 ident: BFnature25170_CR36 publication-title: Nature doi: 10.1038/nature12209 – volume: 110 start-page: 251 year: 2002 ident: BFnature25170_CR12 publication-title: Cell doi: 10.1016/S0092-8674(02)00825-5 – volume: 342 start-page: 1243417 year: 2013 ident: BFnature25170_CR18 publication-title: Science doi: 10.1126/science.1243417 – reference: 29666473 - Cell Death Differ. 2018 Jun;25(6):1005-1006. doi: 10.1038/s41418-018-0102-y. – reference: 29352049 - Cancer Discov. 2018 Mar;8(3):261. doi: 10.1158/2159-8290.CD-RW2018-011. |
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| Snippet | REV-ERBs, nuclear hormone receptors that regulate transcription as part of the circadian clock cell machinery, inhibit autophagy and lipogenesis in... The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are... The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response 1 , 2 . Perturbations of these processes are... |
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| Title | Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence |
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