Evidence map›Paper›PMID 23051914›Full record

ArticleAutophagy2012

Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation.

Weiyang He, Qiong Wang, Jennings Xu, Xiuling Xu, Mabel T Padilla, Guosheng Ren, Xin Gou, Yong Lin

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

95 citing papers in PubMed, 156 citations in OpenAlex.

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35 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

8 authors at 4 institutions in 2 countries.

Weiyang HeDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Qiong Wang
Jennings Xu
Xiuling Xu
Mabel T Padilla
Guosheng Ren
Xin Gou
Yong Lin
Radiology Associates of Albuquerque · USChongqing Medical University · CNLovelace Respiratory Research Institute · USMolecular Oncology (United States) · US

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
NIEHS NIH HHS R01 ES017328NIEHS NIH HHS R01ES017328
6 · The paper itself

Abstract

Although it is known that tumor necrosis factor-related apoptosis-inducing ligand (TNFSF10/TRAIL) induces autophagy, the mechanism by which autophagy is activated by TNFSF10 is still elusive. In this report, we show evidence that TRAF2- and RIPK1-mediated MAPK8/JNK activation is required for TNFSF10-induced cytoprotective autophagy. TNFSF10 activated autophagy rapidly in cancer cell lines derived from lung, bladder and prostate tumors. Blocking autophagy with either pharmacological inhibitors or siRNAs targeting the key autophagy factors BECN1/Beclin 1 or ATG7 effectively increased TNFSF10-induced apoptotic cytotoxicity, substantiating a cytoprotective role for TNFSF10-induced autophagy. Blocking MAPK8 but not NFκB effectively blocked autophagy, suggesting that MAPK8 is the main pathway for TNFSF10-induced autophagy. In addition, blocking MAPK8 effectively inhibited degradation of BCL2L1/Bcl-xL and reduction of the autophagy-suppressing BCL2L1-BECN1complex. Knockdown of TRAF2 or RIPK1 effectively suppressed TNFSF10-induced MAPK8 activation and autophagy. Furthermore, suppressing autophagy inhibited expression of antiapoptosis factors BIRC2/cIAP1, BIRC3/cIAP2, XIAP and CFLAR/c-FLIP and increased the formation of TNFSF10-induced death-inducing signaling complex (DISC). These results reveal a critical role for the MAPK8 activation pathway through TRAF2 and RIPK1 for TNFSF10-induced autophagy that blunts apoptosis in cancer cells. Thus, suppression of MAPK8-mediated autophagy could be utilized for sensitizing cancer cells to therapy with TNFSF10.

Indexed as

Signal TransductionApoptosisApoptosis Regulatory ProteinsAutophagybcl-X ProteinBeclin-1Cell Line, TumorCell SurvivalCytoprotectionEnzyme ActivationHumansJNK Mitogen-Activated Protein KinasesMembrane ProteinsProteolysisReceptor-Interacting Protein Serine-Threonine KinasesTNF Receptor-Associated Factor 2Apoptosis Regulatory ProteinsBCL2L1 protein, humanbcl-X ProteinBeclin-1BECN1 protein, humanJNK Mitogen-Activated Protein KinasesMembrane ProteinsReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanTNF Receptor-Associated Factor 2TNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID23051914
PMCPMC3541290
OpenAlexW2041508767

What OpenQuestion holds

Textmetadata
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.