Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells.

Abstract:

:Salinomycin is perhaps the first promising compound that was discovered through high throughput screening in cancer stem cells. This novel agent can selectively eliminate breast and other cancer stem cells, though the mechanism of action remains unclear. In this study, we found that salinomycin induced autophagy in human non-small cell lung cancer (NSCLC) cells. Furthermore, we demonstrated that salinomycin stimulated endoplasmic reticulum stress and mediated autophagy via the ATF4-DDIT3/CHOP-TRIB3-AKT1-MTOR axis. Moreover, we found that the autophagy induced by salinomycin played a prosurvival role in human NSCLC cells and attenuated the apoptotic cascade. We also showed that salinomycin triggered more apoptosis and less autophagy in A549 cells in which CDH1 expression was inhibited, suggesting that the inhibition of autophagy might represent a promising strategy to target cancer stem cells. In conclusion, these findings provide evidence that combination treatment with salinomycin and pharmacological autophagy inhibitors will be an effective therapeutic strategy for eliminating cancer cells as well as cancer stem cells.

journal_name

Autophagy

journal_title

Autophagy

authors

Li T,Su L,Zhong N,Hao X,Zhong D,Singhal S,Liu X

doi

10.4161/auto.24632

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

1057-68

issue

7

eissn

1554-8627

issn

1554-8635

pii

24632

journal_volume

9

pub_type

杂志文章
  • Folding into an autophagosome: ATG5 sheds light on how plants do it.

    abstract::Autophagosomes arise in yeast and animals from the sealing of a cup-shaped double-membrane precursor, the phagophore. The concerted action of about 30 evolutionarily conserved autophagy related (ATG) proteins lies at the core of this process. However, the mechanisms allowing phagophore generation and its differentiati...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.29962

    authors: Le Bars R,Marion J,Satiat-Jeunemaitre B,Bianchi MW

    更新日期:2014-10-01 00:00:00

  • Mutant HTT (huntingtin) impairs mitophagy in a cellular model of Huntington disease.

    abstract::The precise degradation of dysfunctional mitochondria by mitophagy is essential for maintaining neuronal homeostasis. HTT (huntingtin) can interact with numerous other proteins and thereby perform multiple biological functions within the cell. In this study, we investigated the role of HTT during mitophagy and analyze...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1728096

    authors: Franco-Iborra S,Plaza-Zabala A,Montpeyo M,Sebastian D,Vila M,Martinez-Vicente M

    更新日期:2020-02-24 00:00:00

  • Amelioration of protein misfolding disease by rapamycin: translation or autophagy?

    abstract::Rapamycin is an inhibitor of mTOR, a key component of the mTORC1 complex that controls the growth and survival of cells in response to growth factors, nutrients, energy balance and stresses. The downstream targets of mTORC1 include ribosome biogenesis, transcription, translation and macroautophagy. Recently it was pro...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6059

    authors: Wyttenbach A,Hands S,King MA,Lipkow K,Tolkovsky AM

    更新日期:2008-05-01 00:00:00

  • Autophagy-independent incorporation of GFP-LC3 into protein aggregates is dependent on its interaction with p62/SQSTM1.

    abstract::LC3 is a widely used marker of autophagosomes in mammalian cells. However, in addition to its autophagosomal localization, GFP-LC3 is often found associated with protein aggregates that are formed in an autophagy-independent manner. In addition, LC3 directly interacts with p62/SQSTM1 (hereafter named p62), a common co...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6823

    authors: Shvets E,Elazar Z

    更新日期:2008-11-01 00:00:00

  • Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila.

    abstract::Autophagy is involved with the turnover of intracellular components and the management of stress responses. Genetic studies in mice have shown that suppression of neuronal autophagy can lead to the accumulation of protein aggregates and neurodegeneration. However, no study has shown that increasing autophagic gene exp...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5269

    authors: Simonsen A,Cumming RC,Brech A,Isakson P,Schubert DR,Finley KD

    更新日期:2008-02-01 00:00:00

  • Autophagy is required for the degeneration of the ovarian follicular epithelium in higher Diptera.

    abstract::Autophagy is a major pathway for the degradation of long-lived proteins and cytoplasmic organelles and an essential part of programmed cell death, as well. Our findings indicate that programmed cell death of the ovarian follicle cells in the higher Diptera species Bactrocera oleae and Ceratitis capitata manifests feat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.2858

    authors: Nezis IP,Stravopodis DJ,Margaritis LH,Papassideri IS

    更新日期:2006-10-01 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

  • 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

  • Artophagy: the art of autophagy--the Cvt pathway.

    abstract::Science informs art, and art informs science. Both processes involve creativity and imagination, and collaboration between scientists and artists often leads to new insights in both fields. We took advantage of the power of artistic imagery to demonstrate a dynamic cellular process, autophagy. In particular, we depict...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.1.10812

    authors: Goodsell DS,Klionsky DJ

    更新日期:2010-01-01 00:00:00

  • Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy.

    abstract::Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and prote...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1360466

    authors: Kaverina N,Borovjagin AV,Kadagidze Z,Baryshnikov A,Baryshnikova M,Malin D,Ghosh D,Shah N,Welch DR,Gabikian P,Karseladze A,Cobbs C,Ulasov IV

    更新日期:2017-01-01 00:00:00

  • TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition.

    abstract::The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arre...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1429875

    authors: Lima S,Takabe K,Newton J,Saurabh K,Young MM,Leopoldino AM,Hait NC,Roberts JL,Wang HG,Dent P,Milstien S,Booth L,Spiegel S

    更新日期:2018-01-01 00:00:00

  • Dual role of Atg1 in regulation of autophagy-specific PAS assembly in Saccharomyces cerevisiae.

    abstract::Most autophagy-related (Atg) proteins are assembled at the phagophore assembly site or pre-autophagosomal structure (PAS), which is a potential site for vesicle formation during vegetative or starvation conditions. To understand the initial step of vesicle formation, it is important to know how Atg proteins are recrui...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6375

    authors: Cheong H,Klionsky DJ

    更新日期:2008-07-01 00:00:00

  • The Golgi as a potential membrane source for autophagy.

    abstract::In macroautophagy (hereafter autophagy), a morphological hallmark is the formation of double-membrane vesicles called autophagosomes that sequester and deliver cytoplasmic components to the lysosome/vacuole for degradation. This process begins with an initial sequestering compartment, the phagophore, which expands int...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13009

    authors: Geng J,Klionsky DJ

    更新日期:2010-10-01 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

  • 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

  • Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase.

    abstract::Autophagy, a catabolic pathway of lysosomal degradation, acts not only as an efficient recycle and survival mechanism during cellular stress, but also as an anti-infective machinery. The human pathogen Staphylococcus aureus (S. aureus) was originally considered solely as an extracellular bacterium, but is now recogniz...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1226732

    authors: Neumann Y,Bruns SA,Rohde M,Prajsnar TK,Foster SJ,Schmitz I

    更新日期:2016-11-01 00:00:00

  • Secretory autophagy holds the key to lysozyme secretion during bacterial infection of the intestine.

    abstract::In 2013, Dr. Lora Hooper and colleagues described the induction of antibacterial macroautophagy/autophagy in intestinal epithelial cells as a cytoprotective host defense mechanism against invading Salmonella enterica serovar Typhimurium (S. Typhimurium). Canonical autophagy functions in a primarily degradative capacit...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2017.1401425

    authors: Delorme-Axford E,Klionsky DJ

    更新日期:2018-01-01 00:00:00

  • Mice deficient in the Vici syndrome gene Epg5 exhibit features of retinitis pigmentosa.

    abstract::Autophagy helps to maintain cellular homeostasis by removing misfolded proteins and damaged organelles, and generally acts as a cytoprotective mechanism for neuronal survival. Here we showed that mice deficient in the Vici syndrome gene Epg5, which is required for autophagosome maturation, show accumulation of ubiquit...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1238554

    authors: Miao G,Zhao YG,Zhao H,Ji C,Sun H,Chen Y,Zhang H

    更新日期:2016-12-01 00:00:00

  • Autophagy as a rescue mechanism in efavirenz-induced mitochondrial dysfunction: a lesson from hepatic cells.

    abstract::Efavirenz (EFV) is the most widely used non-nucleoside reverse transcriptase inhibitor applied in highly active antiretroviral therapy (HAART), the combined pharmacological treatment of the human immunodeficiency virus infection. Its use has been associated with the development of several adverse events including hepa...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.11.17653

    authors: Apostolova N,Gomez-Sucerquia LJ,Gortat A,Blas-Garcia A,Esplugues JV

    更新日期:2011-11-01 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

  • Crosstalk between lysine methylation and phosphorylation of ATG16L1 dictates the apoptosis of hypoxia/reoxygenation-induced cardiomyocytes.

    abstract::Post-translational modifications of autophagy-related (ATG) genes are necessary to modulate their functions. However, ATG protein methylation and its physiological role have not yet been elucidated. The methylation of non-histone proteins by SETD7, a SET domain-containing lysine methyltransferase, is a novel regulator...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1389357

    authors: Song H,Feng X,Zhang M,Jin X,Xu X,Wang L,Ding X,Luo Y,Lin F,Wu Q,Liang G,Yu T,Liu Q,Zhang Z

    更新日期:2018-01-01 00:00:00

  • Autophagy mediates phosphatidylserine exposure and phagosome degradation during apoptosis through specific functions of GABARAP/LGG-1 and LC3/LGG-2.

    abstract::Phagocytosis and macroautophagy/autophagy are 2 processes involved in lysosome-mediated clearance of extracellular and intracellular components, respectively. Recent studies have identified the recruitment of the autophagic protein LC3 during phagocytosis of apoptotic corpses in what is now called LC3-associated phago...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1512452

    authors: Jenzer C,Simionato E,Largeau C,Scarcelli V,Lefebvre C,Legouis R

    更新日期:2019-02-01 00:00:00

  • Implications of autophagy in anthrax pathogenicity.

    abstract::The etiological agent for anthrax is Bacillus anthracis, which produces lethal toxin (LT) that exerts a myriad of effects on many immune cells. In our previous study, it was demonstrated that LT and protective antigen (PA) induce autophagy in mammalian cells. Preliminary results suggest that autophagy may function as ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.5.8567

    authors: Tan YK,Vu HA,Kusuma CM,Wu A

    更新日期:2009-07-01 00:00:00

  • DAMPs and autophagy: cellular adaptation to injury and unscheduled cell death.

    abstract::Autophagy is a lysosome-mediated catabolic process involving the degradation of intracellular contents (e.g., proteins and organelles) as well as invading microbes (e.g., parasites, bacteria and viruses). Multiple forms of cellular stress can stimulate this pathway, including nutritional imbalances, oxygen deprivation...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.23691

    authors: Zhang Q,Kang R,Zeh HJ 3rd,Lotze MT,Tang D

    更新日期:2013-04-01 00:00:00

  • Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans.

    abstract::Autophagy is a conserved membrane trafficking pathway that mediates the delivery of cytoplasmic substrates to the lysosome for degradation. Impaired autophagic function is implicated in the pathology of various neurodegenerative diseases. We have generated transgenic C. elegans that express human beta-amyloid peptide ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.4776

    authors: Florez-McClure ML,Hohsfield LA,Fonte G,Bealor MT,Link CD

    更新日期:2007-11-01 00:00:00

  • Inhibitory effect of intracellular lipid load on macroautophagy.

    abstract::Degradation of intracellular components via macroautophagy is a complex multistep process that starts with the sequestration of cytosolic cargo in a de novo formed double-membrane vesicle or autophagosome. This compartment acquires the hydrolases required for cargo digestion by fusion with lysosomes. In contrast to th...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1096/fj.09-144519

    authors: Koga H,Kaushik S,Cuervo AM

    更新日期:2010-08-01 00:00:00

  • The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation.

    abstract::The initiation of macroautophagy/autophagy is tightly regulated by the upstream ULK1 kinase complex, which affects many downstream factors including the PtdIns3K complex. The phosphorylation of the right position at the right time on downstream molecules is governed by proper complex formation. One component of the UL...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1504716

    authors: Kim BW,Jin Y,Kim J,Kim JH,Jung J,Kang S,Kim IY,Kim J,Cheong H,Song HK

    更新日期:2018-01-01 00:00:00

  • BNIP3L-dependent mitophagy accounts for mitochondrial clearance during 3 factors-induced somatic cell reprogramming.

    abstract::Induced pluripotent stem cells (iPSCs) have fewer and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogr...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1338545

    authors: Xiang G,Yang L,Long Q,Chen K,Tang H,Wu Y,Liu Z,Zhou Y,Qi J,Zheng L,Liu W,Ying Z,Fan W,Shi H,Li H,Lin X,Gao M,Liu J,Bao F,Li L,Duan L,Li M,Liu X

    更新日期:2017-09-02 00:00:00

  • Autophagy proteins are not universally required for phagosome maturation.

    abstract::Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome ma...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1191724

    authors: Cemma M,Grinstein S,Brumell JH

    更新日期:2016-09-01 00:00:00

  • Autophagy contributes to regulation of nuclear dynamics during vegetative growth and hyphal fusion in Fusarium oxysporum.

    abstract::In the fungal pathogen Fusarium oxysporum, vegetative hyphal fusion triggers nuclear mitotic division in the invading hypha followed by migration of a nucleus into the receptor hypha and degradation of the resident nucleus. Here we examined the role of autophagy in fusion-induced nuclear degradation. A search of the F...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/15548627.2014.994413

    authors: Corral-Ramos C,Roca MG,Di Pietro A,Roncero MI,Ruiz-Roldán C

    更新日期:2015-01-01 00:00:00