The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer.

Abstract:

:Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients. Further, we evaluated the potential associations of these genes with subsequent BM development. Lung cancer cell lines stably transfected with ATG16L1: rs2241880 (T300A) were established. Mouse models of brain metastasis were developed using cells transfected with ATG16L1-300T or ATG16L1-300A. ATG10: rs10036653 and ATG16L1: rs2241880 were significantly associated with a decreased risk of BM (respective hazard ratios [HRs]=0.596, 95% confidence interval [CI] 0.398-0.894, P = 0.012; and HR = 0. 655, 95% CI 0.438-0.978, P = 0.039, respectively). ATG12: rs26532 was significantly associated with an increased risk of BM (HR=1.644, 95% CI 1.049-2.576, P = 0.030). Invasion and migration assays indicated that transfection with ATG16L1-300T (vs. 300A) stimulated the migration of A549 cells. An in vivo metastasis assay revealed that transfection with ATG16L1-300T (vs. 300A) significantly increased brain metastasis. Our results indicate that genetic variations in autophagy-related genes can predict BM and that genome analysis would facilitate stratification of patients for BM prevention trials.

journal_name

Autophagy

journal_title

Autophagy

authors

Li QX,Zhou X,Huang TT,Tang Y,Liu B,Peng P,Sun L,Wang YH,Yuan XL

doi

10.1080/15548627.2017.1308997

subject

Has Abstract

pub_date

2017-06-03 00:00:00

pages

1053-1063

issue

6

eissn

1554-8627

issn

1554-8635

journal_volume

13

pub_type

杂志文章
  • Perturbation of autophagic pathway by hepatitis C virus.

    abstract::Autophagy removes long-lived proteins and damaged organelles and is important for maintaining cellular homeostasis. It can also serve in innate immunity to remove intracellular pathogens. As such, viruses have evolved different mechanisms to subvert this innate immune response. We have recently demonstrated that hepat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6566

    authors: Sir D,Liang C,Chen WL,Jung JU,Ou JH

    更新日期:2008-08-01 00:00:00

  • Context effect: microRNA-10b in cancer cell proliferation, spread and death.

    abstract::Single microRNA (miRNA) can regulate expression of several or multiple principal targets in a specific microenvironment. In different cellular contexts, the same miRNA may exhibit diverse functions, depending on the repertoire and stoichiometry of its direct mRNA targets. For instance, in breast cancer, microRNA-10b (...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.11.17371

    authors: Gabriely G,Teplyuk NM,Krichevsky AM

    更新日期:2011-11-01 00:00:00

  • Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence.

    abstract::Deficiency in decidualization has been widely regarded as an important cause of spontaneous abortion. Generalized decidualization also includes massive infiltration and enrichment of NK cells. However, the underlying mechanism of decidual NK (dNK) cell residence remains largely unknown. Here, we observe that the incre...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1833515

    authors: Lu H,Yang HL,Zhou WJ,Lai ZZ,Qiu XM,Fu Q,Zhao JY,Wang J,Li DJ,Li MQ

    更新日期:2020-11-01 00:00:00

  • The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations.

    abstract::Mitochondrial dysfunction is an early sign of many neurodegenerative diseases. Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy). PINK1 kinase activity is needed for prompt and efficient Parkin...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13286

    authors: Geisler S,Holmström KM,Treis A,Skujat D,Weber SS,Fiesel FC,Kahle PJ,Springer W

    更新日期:2010-10-01 00:00:00

  • Retromer regulates the lysosomal clearance of MAPT/tau.

    abstract::The macroautophagy/autophagy-lysosome axis enables the clearance and degradation of cytoplasmic components including protein aggregates, damaged organelles and invading pathogens. Protein aggregation and lysosomal system dysfunction in the brain are common features of several late-onset neurological disorders includin...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1821545

    authors: Carosi JM,Hein LK,van den Hurk M,Adams R,Milky B,Singh S,Bardy C,Denton D,Kumar S,Sargeant TJ

    更新日期:2020-09-22 00:00:00

  • The Rag GTPase-Ragulator complex attenuates TOR complex 1 signaling in fission yeast.

    abstract::Target of rapamycin complex 1 (TORC1) is an evolutionarily conserved protein kinase complex, whose activation in response to nutrients suppresses autophagy. In mammalian cells, amino-acid stimuli induce lysosomal translocation and activation of MTORC1 through the RRAG GTPase heterodimer, which is tethered to the surfa...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2018.1444313

    authors: Fukuda T,Shiozaki K

    更新日期:2018-01-01 00:00:00

  • Mouse infection by Legionella, a model to analyze autophagy.

    abstract::Autophagy is a conserved membrane traffic pathway that equips eukaryotic cells to capture cytoplasmic components within a double-membrane vacuole, or autophagosome, for delivery to lysosomes. Although best known as a mechanism to survive starvation, autophagy is now recognized to combat infection by a variety of micro...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.2831

    authors: Dubuisson JF,Swanson MS

    更新日期:2006-07-01 00:00:00

  • PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis.

    abstract::Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway h...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1017190

    authors: Ito S,Araya J,Kurita Y,Kobayashi K,Takasaka N,Yoshida M,Hara H,Minagawa S,Wakui H,Fujii S,Kojima J,Shimizu K,Numata T,Kawaishi M,Odaka M,Morikawa T,Harada T,Nishimura SL,Kaneko Y,Nakayama K,Kuwano K

    更新日期:2015-01-01 00:00:00

  • IRGM Links Autoimmunity to Autophagy.

    abstract::IRGM is a genetic risk factor for several autoimmune diseases. However, the mechanism of IRGM-mediated protection in autoimmunity remains undetermined. The abnormal activation of type I interferon (IFN) response is one of the significant factors in the pathogenesis of several autoimmune diseases. In our recent study, ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1810920

    authors: Nath P,Jena KK,Mehto S,Chauhan NR,Sahu R,Dhar K,Srinivas K,Chauhan S,Chauhan S

    更新日期:2020-08-19 00:00:00

  • Guidelines for the use and interpretation of assays for monitoring autophagy.

    abstract::In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update the...

    journal_title:Autophagy

    pub_type: 指南,杂志文章

    doi:10.4161/auto.19496

    authors: Klionsky DJ,Abdalla FC,Abeliovich H,Abraham RT,Acevedo-Arozena A,Adeli K,Agholme L,Agnello M,Agostinis P,Aguirre-Ghiso JA,Ahn HJ,Ait-Mohamed O,Ait-Si-Ali S,Akematsu T,Akira S,Al-Younes HM,Al-Zeer MA,Albert ML,Albin RL

    更新日期:2012-04-01 00:00:00

  • Suppressing the dark side of autophagy.

    abstract::A wide variety of genetic, pharmacological and nutrient manipulations that extend lifespan in model organisms do so in a manner dependent upon increased autophagic flux. However, our recent findings suggest that when mitochondrial membrane integrity is compromised, macroautophagy/autophagy can be detrimental. In C. el...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1644077

    authors: Zhou B,Soukas AA

    更新日期:2019-10-01 00:00:00

  • Decreased neuronal autophagy in HIV dementia: a mechanism of indirect neurotoxicity.

    abstract::Many recent studies indicate that dysregulation of autophagy is a common feature of many neurodegenerative diseases. The HIV-1-associated neurological disorder is an acquired cognitive and motor disease that includes a severe neurodegenerative dementia. We find that the neurodegeneration seen in the brain in HIV-1 inf...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6805

    authors: Alirezaei M,Kiosses WB,Fox HS

    更新日期:2008-10-01 00:00:00

  • Exploiting cell death pathways by an E. coli cytotoxin: autophagy as a double-edged sword for the host.

    abstract::Cytotoxic necrotizing factor 1 is a bacterial protein toxin from Escherichia coli that is able to activate the Rho GTPases and to hinder apoptosis and mitotic catastrophe. Upon exposure to toxin, cells undergo a complex framework of changes, including cytoskeleton remodeling and multinucleation. These cells also show ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.2965

    authors: Fiorentini C,Malorni W

    更新日期:2006-10-01 00:00:00

  • Autophagy proteins promote hepatitis C virus replication.

    abstract::Autophagy is a fundamental process for anti-viral defense. Not surprisingly, viruses have developed strategies to subvert or use autophagy for their own benefit. In cell culture, autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Autophagy proteins are required for tran...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.8.10219

    authors: Dreux M,Chisari FV

    更新日期:2009-11-01 00:00:00

  • Q6, a novel hypoxia-targeted drug, regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma.

    abstract::Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes. Although therapeutically targeting these hypoxic environments has been proposed for many years, to date no approaches have shown the therapeutic value to gain regulatory approval. Here, we demonstrated that a novel h...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26838

    authors: Liu XW,Cai TY,Zhu H,Cao J,Su Y,Hu YZ,He QJ,Yang B

    更新日期:2014-01-01 00:00:00

  • Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial.

    abstract::A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorder...

    journal_title:Autophagy

    pub_type: 临床试验,杂志文章

    doi:10.1080/15548627.2016.1231279

    authors: Castagnaro S,Pellegrini C,Pellegrini M,Chrisam M,Sabatelli P,Toni S,Grumati P,Ripamonti C,Pratelli L,Maraldi NM,Cocchi D,Righi V,Faldini C,Sandri M,Bonaldo P,Merlini L

    更新日期:2016-12-01 00:00:00

  • Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome.

    abstract::Based on a functional categorization, proteins may be grouped into three types and sorted to either the proteasome or the macroautophagy pathway for degradation. The two pathways are mechanistically connected but their capacity seems different. Macroautophagy can degrade all forms of misfolded proteins whereas proteas...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.5190

    authors: Ding WX,Yin XM

    更新日期:2008-02-01 00:00:00

  • MTOR inhibition attenuates DNA damage and apoptosis through autophagy-mediated suppression of CREB1.

    abstract::Hyperactivation of mechanistic target of rapamycin (MTOR) is a common feature of human cancers, and MTOR inhibitors, such as rapamycin, are thus becoming therapeutics in targeting certain cancers. However, rapamycin has also been found to compromise the efficacy of chemotherapeutics to cells with hyperactive MTOR. Her...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26447

    authors: Wang Y,Hu Z,Liu Z,Chen R,Peng H,Guo J,Chen X,Zhang H

    更新日期:2013-12-01 00:00:00

  • RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye.

    abstract::Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1380124

    authors: Muniz-Feliciano L,Doggett TA,Zhou Z,Ferguson TA

    更新日期:2017-01-01 00:00:00

  • Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

    abstract::Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated eth...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.18997

    authors: Guo R,Hu N,Kandadi MR,Ren J

    更新日期:2012-04-01 00:00:00

  • Role for nanomaterial-autophagy interaction in neurodegenerative disease.

    abstract::Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nanotechnology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated e...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7142

    authors: Stern ST,Johnson DN

    更新日期:2008-11-01 00:00:00

  • BECN1 is a new driver of ferroptosis.

    abstract::Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferropto...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2018.1513758

    authors: Kang R,Zhu S,Zeh HJ,Klionsky DJ,Tang D

    更新日期:2018-01-01 00:00:00

  • Localized de novo phospholipid synthesis drives autophagosome biogenesis.

    abstract::During (macro)autophagy, cells form transient organelles, termed autophagosomes, to target a broad spectrum of substrates for degradation critical to cellular and organismal health. Driven by rapid membrane assembly, an initially small vesicle (phagophore) elongates into a large cup-shaped structure to engulf substrat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1725379

    authors: Schütter M,Graef M

    更新日期:2020-04-01 00:00:00

  • Autophagy maintains cardiac function in the starved adult.

    abstract::To examine the functional significance and detailed morphological characteristics of starvation-induced autophagy in the adult heart, we starved green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice for up to 3 days. Electron microscopy revealed that, after as little as 1...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.7.9297

    authors: Takemura G,Kanamori H,Goto K,Maruyama R,Tsujimoto A,Fujiwara H,Seishima M,Minatoguchi S

    更新日期:2009-10-01 00:00:00

  • Autophagy as a mechanism of antiviral defense at the maternal-fetal interface.

    abstract::Mechanisms to protect against viral infections are crucial during pregnancy as maternal-fetal transmission can have serious pathological outcomes, including fetal infection and its sequelae, such as growth restriction, birth defects, and/or fetal death. The trophoblast forms the interface between the feto-placental un...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26558

    authors: Delorme-Axford E,Bayer A,Sadovsky Y,Coyne CB

    更新日期:2013-12-01 00:00:00

  • Autophagy, Inflammation, and Metabolism (AIM) Center in its second year.

    abstract::The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally...

    journal_title:Autophagy

    pub_type: 历史文章,杂志文章

    doi:10.1080/15548627.2019.1634444

    authors: Deretic V,Prossnitz E,Burge M,Campen MJ,Cannon J,Liu KJ,Liu M,Hall P,Sklar LA,Allers L,Mariscal L,Garcia SA,Weaver J,Baehrecke EH,Behrends C,Cecconi F,Codogno P,Chen GC,Elazar Z,Eskelinen EL,Fourie B,Gozuacik D

    更新日期:2019-10-01 00:00:00

  • Autophagy: The missing link between non-enzymatically glycated proteins inducing apoptosis and premature senescence of endothelial cells?

    abstract::In a series of studies into the fate of endothelial cells exposed to non-enzymatically glycated collagen I, a model of cytotoxic molecules relevant to diabetic vasculopathy, we demonstrate that cells either undergo apoptosis or become prematurely senescent despite relatively spared telomeres and telomerase activity. O...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5904

    authors: Patschan S,Goligorsky MS

    更新日期:2008-05-01 00:00:00

  • Autophagy: a new player in hepatic stellate cell activation.

    abstract::Hepatic stellate cell (HSC) activation, the transition from a resident quiescent HSC to a myofibroblastic collagen-producing HSC, is a fundamental feature of liver fibrosis. Autophagy has been implicated in major liver pathologies, such as HCV infection and hepatocarcinoma. However, its role in HSC biology is largely ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.8.1.18105

    authors: Thoen LF,Guimarães EL,Grunsven LA

    更新日期:2012-01-01 00:00:00

  • Cell-autonomous, paracrine and neuroendocrine feedback regulation of autophagy by DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein): the obesity factor.

    abstract::DBI/ACBP (diazepam binding protein, acyl-CoA binding protein) participates in the regulation of fatty acid metabolism when it is localized within cells, whereas outside of cells it acts as a diazepam-binding protein. Recent results indicate that many different mammalian cell types release DBI/ACBP upon in vitro or in ...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2019.1662585

    authors: Bravo-San Pedro JM,Sica V,Martins I,Anagnostopoulos G,Maiuri C,Kroemer G

    更新日期:2019-11-01 00:00:00

  • SYK regulates macrophage MHC-II expression via activation of autophagy in response to oxidized LDL.

    abstract::Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxid...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1037061

    authors: Choi SH,Gonen A,Diehl CJ,Kim J,Almazan F,Witztum JL,Miller YI

    更新日期:2015-01-01 00:00:00