Evidence map›Paper›PMID 23831571›Full record

ArticleOncogene2014

A JNK-mediated autophagy pathway that triggers c-IAP degradation and necroptosis for anticancer chemotherapy.

W He, Q Wang, B Srinivasan, J Xu, M T Padilla, Z Li, X Wang, Y Liu, X Gou, H-M Shen and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023
    Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

W He1] Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA [2] Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Q Wang1] Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA [2] Laboratory of Molecular and Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
B SrinivasanDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
J XuMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
M T PadillaMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Z LiMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
X WangLaboratory of Molecular and Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Y LiuMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
X GouDepartment of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
H-M ShenDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
C XingDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Y LinMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Lovelace Respiratory Research Institute · USUniversity of Minnesota · USChongqing Medical University · CNNational University of Singapore · SGSichuan University · CN

Funding

Bridging Inflammation and Cigarette Smoke-associated Lung Carcinogenesis by MUC1R01ES017328 · NIEHS · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI LIN, YONG · 2010 to 2014
$2.2M
An NF-kB inhibitor as a post-carcinogen lung cancer chemopreventive agentR03CA156301 · NCI · UNIVERSITY OF MINNESOTA · PI XING, CHENGGUO · 2011 to 2012
$145k
NCI NIH HHS R03 CA156301NCI NIH HHS R03CA156301NIEHS NIH HHS R01 ES017328NIEHS NIH HHS R01ES017328
6 · The paper itself

Abstract

Killing cancer cells through the induction of apoptosis is one of the main mechanisms of chemotherapy. However, numerous cancer cells have primary or acquired apoptosis resistance, resulting in chemoresistance. In this study, using a novel chalcone derivative chalcone-24 (Chal-24), we identified a novel anticancer mechanism through autophagy-mediated necroptosis (RIP1- and RIP3-dependent necrosis). Chal-24 potently killed different cancer cells with induction of necrotic cellular morphology while causing no detectable caspase activation. Blocking the necroptosis pathway with either necrostatin-1 or by knockdown of RIP1 and RIP3 effectively blocked the cytotoxicity of Chal-24, suggesting that Chal-24-induced cell death is associated with necroptosis. Chal-24 robustly activated JNK and ERK and blockage of which effectively suppressed Chal-24-induced cytotoxicity. In addition, Chal-24 strongly induced autophagy that is dependent on JNK-mediated phosphorylation of Bcl-2 and Bcl-xL and dissociation of Bcl-2 or Bcl-xL from Beclin-1. Importantly, suppression of autophagy, with either pharmacological inhibitors or small interfering RNAs targeting the essential autophagy components ATG7 and Beclin-1, effectively attenuated Chal-24-induced cell death. Furthermore, we found that autophagy activation resulted in c-IAP1 and c-IAP2 degradation and formation of the Ripoptosome that contributes to necroptosis. These results thus establish a novel mechanism for killing cancer cells that involves autophagy-mediated necroptosis, which may be employed for overcoming chemoresistance.

Indexed as

Antineoplastic AgentsApoptosisApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 7Baculoviral IAP Repeat-Containing 3 ProteinBeclin-1Cell Line, TumorChalconesDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansImidazolesIndolesInhibitor of Apoptosis Proteins3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-oneAGFG1 protein, humanAntineoplastic AgentsApoptosis Regulatory ProteinsATG7 protein, humanAutophagy-Related Protein 7Baculoviral IAP Repeat-Containing 3 ProteinBeclin-1BECN1 protein, humanBIRC2 protein, humanBIRC3 protein, humanChalconesImidazolesIndolesInhibitor of Apoptosis ProteinsMAP Kinase Kinase 4Membrane Proteinsnecrostatin-1Nuclear Pore Complex ProteinsReceptor-Interacting Protein Serine-Threonine KinasesRIPK3 protein, humanRNA-Binding ProteinsRNA, Small InterferingUbiquitin-Activating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID23831571
PMCPMC3912228
OpenAlexW2016036036

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.