The interplay between PRKCI/PKCλ/ι, SQSTM1/p62, and autophagy orchestrates the oxidative metabolic response that drives liver cancer.

Abstract:

:Hepatocellular carcinoma (HCC) is the consequence of chronic liver damage caused by the excessive generation of reactive oxygen species (ROS). To mitigate the deleterious effects of ROS, cells activate the transcription factor NFE2L2/NRF2, which is constitutively degraded through its partner KEAP1. The inactivation of KEAP1 by ROS results in the upregulation of NFE2L2, which leads to the upregulation of critical detoxifying molecules that serve to keep ROS at tolerable levels in order to maintain cell viability. It is thought that this mechanism allows cells to accumulate mutations, which together with the additional pro-tumorigenic and pro-survival effects of NFE2L2 activation, promote cancer initiation and progression. Germane to this phenomenon is macroautophagy/autophagy, which under homeostatic conditions has also been proposed to serve as a detoxifying mechanism by clearing up toxic aggregates and damaged organelles. Our recent data establish a new paradigm for the role that autophagy plays in HCC development.

journal_name

Autophagy

journal_title

Autophagy

authors

Moscat J,Diaz-Meco MT

doi

10.1080/15548627.2020.1797290

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1915-1917

issue

10

eissn

1554-8627

issn

1554-8635

journal_volume

16

pub_type

评论,杂志文章
  • Autophagic degeneration and death of cardiomyocytes in heart failure.

    abstract::Numerous cardiomyocytes were found to show autophagic vacuolar degeneration in the UM-X7.1 hamster model of human dilated cardiomyopathy, and autophagy-related proteins--i.e., ubiquitin, cathepsin D and Rab7--were upregulated in those hearts. Importantly, Evans blue-positive cardiomyocytes with leaky plasma membranes ...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.2608

    authors: Takemura G,Miyata S,Kawase Y,Okada H,Maruyama R,Fujiwara H

    更新日期:2006-07-01 00:00:00

  • Role of actin in shaping autophagosomes.

    abstract::One of the main unanswered questions regarding the early steps of macroautophagy/autophagy is the mechanism of membrane-modeling events required for autophagosome formation. Three independent studies have recently revealed an actin cytoskeleton involvement in this process, providing significant details regarding the r...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1236877

    authors: Zientara-Rytter K,Subramani S

    更新日期:2016-12-01 00:00:00

  • In vivo imaging of autophagy in a mouse stroke model.

    abstract::Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 ligh...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.8.13427

    authors: Tian F,Deguchi K,Yamashita T,Ohta Y,Morimoto N,Shang J,Zhang X,Liu N,Ikeda Y,Matsuura T,Abe K

    更新日期:2010-11-01 00:00:00

  • Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis.

    abstract::Autophagy and apoptosis are 2 fundamental biological mechanisms that may cooperate or be antagonistic, although both are involved in deciding the fate of cells in physiological or pathological conditions. These 2 mechanisms coexist simultaneously in cells and share common upstream signals and stimuli. Autophagy and ap...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2016.1256522

    authors: Ravegnini G,Sammarini G,Nannini M,Pantaleo MA,Biasco G,Hrelia P,Angelini S

    更新日期:2017-03-04 00:00:00

  • Caspase activation regulates the extracellular export of autophagic vacuoles.

    abstract::The endothelium plays a central role in the regulation of vascular wall cellularity and tone by secreting an array of mediators of importance in intercellular communication. Nutrient deprivation of human endothelial cells (EC) evokes unconventional forms of secretion leading to the release of nanovesicles distinct fro...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.19768

    authors: Sirois I,Groleau J,Pallet N,Brassard N,Hamelin K,Londono I,Pshezhetsky AV,Bendayan M,Hébert MJ

    更新日期:2012-06-01 00:00:00

  • Spread of neuronal degeneration in a dopaminergic, Lrrk-G2019S model of Parkinson disease.

    abstract::Flies expressing the most common Parkinson disease (PD)-related mutation, LRRK2-G2019S, in their dopaminergic neurons show loss of visual function and degeneration of the retina, including mitochondrial abnormalities, apoptosis and autophagy. Since the photoreceptors that degenerate are not dopaminergic, this demonstr...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.24397

    authors: Hindle SJ,Elliott CJ

    更新日期:2013-06-01 00:00:00

  • SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells.

    abstract::SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we repor...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1291479

    authors: Liu H,Ma Y,He HW,Zhao WL,Shao RG

    更新日期:2017-05-04 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

  • Regulation and repurposing of nutrient sensing and autophagy in innate immunity.

    abstract::Nutrients not only act as building blocks but also as signaling molecules. Nutrient-availability promotes cell growth and proliferation and suppresses catabolic processes, such as macroautophagy/autophagy. These effects are mediated by checkpoint kinases such as MTOR (mechanistic target of rapamycin kinase), which is ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1783119

    authors: Sanchez-Garrido J,Shenoy AR

    更新日期:2020-07-05 00:00:00

  • A novel quantitative flow cytometry-based assay for autophagy.

    abstract::Autophagy is a cellular degradation process with an increasingly recognised importance in many biological pathways such as nutrient sensing, stress responses and development. We present a straightforward assay for autophagy which combines the sensitivity of the EGFP-LC3 reporter protein with the throughput capacity an...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.5.12112

    authors: Eng KE,Panas MD,Karlsson Hedestam GB,McInerney GM

    更新日期:2010-07-01 00:00:00

  • Upregulation of SQSTM1/p62 contributes to nickel-induced malignant transformation of human bronchial epithelial cells.

    abstract::Chronic lung inflammation is accepted as being associated with the development of lung cancer caused by nickel exposure. Therefore, identifying the molecular mechanisms that lead to a nickel-induced sustained inflammatory microenvironment that causes transformation of human bronchial epithelial cells is of high signif...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1196313

    authors: Huang H,Zhu J,Li Y,Zhang L,Gu J,Xie Q,Jin H,Che X,Li J,Huang C,Chen LC,Lyu J,Gao J,Huang C

    更新日期:2016-10-02 00:00:00

  • Mitochondrial elongation during autophagy: a stereotypical response to survive in difficult times.

    abstract::Mitochondrial morphological and structural changes play a role in several cellular processes, including apoptosis. We recently reported that mitochondrial elongation is also critical to sustain cell viability during macroautophagy. During macroautophagy unopposed mitochondrial fusion leads to organelle elongation both...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.10.16771

    authors: Gomes LC,Scorrano L

    更新日期:2011-10-01 00:00:00

  • The small GTPase RAB37 functions as an organizer for autophagosome biogenesis.

    abstract::Macroautophagy/autophagy is a catabolic process that is essential for cellular homeostasis. How autophagosomal vesicle forms in a spatio-temporally regulated manner remains elusive. Our recent study revealed that small GTPase, RAB37 (RAB37, member RAS oncogene family), functions as a key organizer of autophagosomal me...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1434374

    authors: Song Y,Shang D,Cheng H,Zhou R

    更新日期:2018-01-01 00:00:00

  • Conformation-dependent recognition of mutant HTT (huntingtin) proteins by selective autophagy.

    abstract::Protein misfolding is the common theme for neurodegenerative disorders including Huntington disease (HD), which is mainly caused by cytotoxicity of the mutant HTT (huntingtin) protein (mHTT). The soluble mHTT has an expanded polyglutamine (polyQ) stretch that may adopt multiple conformations, among which the one recog...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1382783

    authors: Sun X,Fu Y,Pan Y,Lu B

    更新日期:2017-01-01 00:00:00

  • Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway.

    abstract::Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau neurofibrillary tangles. Dysregulated clearance of Aβ largely contributes to its accumulation and plaque formation in the brain. Macroautophagy/autophagy is a l...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2021.1872187

    authors: Wani A,Al Rihani SB,Sharma A,Weadick B,Govindarajan R,Khan SU,Sharma PR,Dogra A,Nandi U,Reddy CN,Bharate SS,Singh G,Bharate SB,Vishwakarma RA,Kaddoumi A,Kumar A

    更新日期:2021-01-19 00:00:00

  • Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy.

    abstract::Oxidative stress-induced granulosa cell (GCs) death represents a common reason for follicular atresia. Follicle-stimulating hormone (FSH) has been shown to prevent GCs from oxidative injury, although the underlying mechanism remains to be elucidated. Here we first report that the suppression of autophagic cell death v...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1327941

    authors: Shen M,Jiang Y,Guan Z,Cao Y,Li L,Liu H,Sun SC

    更新日期:2017-08-03 00:00:00

  • Lysosomal calcium regulates autophagy.

    abstract::Recent evidence has indicated that the lysosome is able to act as a signaling organelle that senses nutrient availability and generates an adaptive response that is important for cellular homeostasis. We recently discovered another example of lysosomal signaling where lysosomal calcium release activates the master aut...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2015.1047130

    authors: Medina DL,Ballabio A

    更新日期:2015-01-01 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

  • Autophagy protects renal tubular cells against cyclosporine toxicity.

    abstract::A major side effect of the powerful immunosuppressive drug cyclosporine (CsA) is the development of a chronic nephrotoxicity whose mechanisms are not fully understood. Recent data suggest that tubular cells play a central role in the pathogenesis of chronic nephropathies. We have shown that CsA is responsible for endo...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6477

    authors: Pallet N,Bouvier N,Legendre C,Gilleron J,Codogno P,Beaune P,Thervet E,Anglicheau D

    更新日期:2008-08-01 00:00:00

  • Impaired autophagy contributes to muscle atrophy in glycogen storage disease type II patients.

    abstract::The autophagy-lysosome system is essential for muscle cell homeostasis and its dysfunction has been linked to muscle disorders that are typically distinguished by massive autophagic buildup. Among them, glycogen storage disease type II (GSDII) is characterized by the presence of large glycogen-filled lysosomes in the ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.21691

    authors: Nascimbeni AC,Fanin M,Masiero E,Angelini C,Sandri M

    更新日期:2012-11-01 00:00:00

  • Targeted therapy for the loss of von Hippel-Lindau in renal cell carcinoma: a novel molecule that induces autophagic cell death.

    abstract::Radiation and conventional cytotoxic chemotherapies are ineffective in treating renal cancer. Approximately 75 percent of renal cell carcinoma (RCC) is associated with an inactivation of the tumor suppressor gene von Hippel-Lindau (VHL). We exploited the possibility of targeting VHL-deficient RCC through synthetic let...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6785

    authors: Turcotte S,Sutphin PD,Giaccia AJ

    更新日期:2008-10-01 00:00:00

  • Purification of autophagosomes from rat hepatocytes.

    abstract::To facilitate the purification of rat liver autophagosomes, isolated rat hepatocytes are first incubated for 2 h at 37°C with vinblastine, which induces autophagosome accumulation by blocking the fusion of these organelles with endosomes and lysosomes. The hepatocytes are then electrodisrupted and homogenized, and the...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.4.11272

    authors: Seglen PO,Brinchmann MF

    更新日期:2010-05-01 00:00:00

  • Autophagy-mediated regulation of macrophages and its applications for cancer.

    abstract::Autophagy is a highly conserved homeostatic pathway that plays an important role in tumor development and progression by acting on cancer cells in a cell-autonomous mechanism. However, the solid tumor is not an island, but rather an ensemble performance that includes nonmalignant stromal cells, such as macrophages. A ...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.26927

    authors: Chen P,Cescon M,Bonaldo P

    更新日期:2014-02-01 00:00:00

  • Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/α-tubulin acetylation.

    abstract::Macroautophagy/autophagy, a fundamental process for degradation of macromolecules and organelles, occurs constitutively at a basal level and is upregulated in response to stress. Whether autophagy regulates protein acetylation and microtubule stability in vascular smooth muscle cells (VSMCs) migration, however, remain...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1707488

    authors: Ouyang C,Mu J,Lu Q,Li J,Zhu H,Wang Q,Zou MH,Xie Z

    更新日期:2020-10-01 00:00:00

  • One step closer to understanding mammalian macroautophagy initiation: Interplay of 2 HORMA architectures in the ULK1 complex.

    abstract::ULK1 and ATG13 assemble with RB1CC1/FIP200 and ATG101 to form a macroautophagy (hereafter autophagy) induction (ULK1) complex in higher eukaryotes. The yeast counterpart, the Atg1 complex, is comprised of Atg1 and Atg13 (ULK1 and ATG13 homologs), Atg17 (a proposed functional homolog of RB1CC1), and either the Atg101 s...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1087635

    authors: Popelka H,Klionsky DJ

    更新日期:2015-11-02 00:00:00

  • The actin cytoskeleton participates in the early events of autophagosome formation upon starvation induced autophagy.

    abstract::Autophagy is a process by which cytoplasmic material is sequestered in a double-membrane vesicle destined for degradation. Nutrient deprivation stimulates the pathway and the number of autophagosomes in the cell increases in response to such stimulus. In the current report we have demonstrated that actin is necessary ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.21459

    authors: Aguilera MO,Berón W,Colombo MI

    更新日期:2012-11-01 00:00:00

  • The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy.

    abstract::Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibi...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1578040

    authors: Zhang M,Liu F,Zhou P,Wang Q,Xu C,Li Y,Bian L,Liu Y,Zhou J,Wang F,Yao Y,Fang Y,Li D

    更新日期:2019-07-01 00:00:00

  • Jurassic PARK2: You eat your mitochondria, and you are what your mitochondria eat.

    abstract::Park2/Parkin is a central mediator of selective mitochondrial autophagy for mitochondrial quality control. We showed in mouse hearts that PINK1/Mfn2/Park2 mediated generalized mitophagy is essential to the normal perinatal transition from fetal mitochondria that prefer carbohydrates as metabolic substrates to adult fa...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1143210

    authors: Dorn GW 2nd

    更新日期:2016-01-01 00:00:00

  • TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy.

    abstract::Upon completion of cytokinesis, the midbody ring is transported asymmetrically into one of the two daughter cells where it becomes a midbody ring derivative that is degraded by autophagy. In this study we showed that the ubiquitin-binding autophagy receptor SQSTM1/p62 and the interacting adaptor protein WDFY3/ALFY for...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26085

    authors: Isakson P,Lystad AH,Breen K,Koster G,Stenmark H,Simonsen A

    更新日期:2013-12-01 00:00:00

  • Macrophages target Salmonella by Lc3-associated phagocytosis in a systemic infection model.

    abstract::Innate immune defense against intracellular pathogens, like Salmonella, relies heavily on the autophagy machinery of the host. This response is studied intensively in epithelial cells, the target of Salmonella during gastrointestinal infections. However, little is known of the role that autophagy plays in macrophages,...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1569297

    authors: Masud S,Prajsnar TK,Torraca V,Lamers GEM,Benning M,Van Der Vaart M,Meijer AH

    更新日期:2019-05-01 00:00:00