Evidence map›Paper›PMID 28513279›Full record

ArticleAutophagy2017

w09, a novel autophagy enhancer, induces autophagy-dependent cell apoptosis via activation of the EGFR-mediated RAS-RAF1-MAP2K-MAPK1/3 pathway.

Pinghu Zhang, Zuguo Zheng, Li Ling, Xiaohui Yang, Ni Zhang, Xue Wang, Maozhi Hu, Yu Xia, Yiwen Ma, Haoran Yang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

41 citing papers in PubMed, 79 citations in OpenAlex.

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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 6 institutions in 1 country.

Pinghu Zhanga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Zuguo Zhenga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Li Linga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Xiaohui Yangb Institute of Chemical Industry of Forestry Products, CAF, National Engineering Laboratory for Biomass Chemical Utilization & Key Laboratory of Forest Chemical Engineering, SFA & Key Lab. of Biomass Energy and Material , Nanjing , China.
Ni Zhanga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Xue Wanga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Maozhi Huc Testing Center , Yangzhou , China.
Yu Xiaa Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Yiwen Maa Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Haoran Yanga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Yunyi Wanga Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & National Nanjing Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China.
Hongqi Liud Infection and Immunity Laboratory, Institute of Medical Biology , Kunming National High-level Biosafety Primate Research Center, Chinese Academy of Medical Science & Peking Union of Medical School , Kunming , China.
State Key Laboratory of Natural MedicineChina Pharmaceutical University · CNNational Center for Drug Screening · CNAnalysis and Testing Centre · CNInstitute of Chemical Industry of Forest Products · CNKunming Institute of Zoology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The EGFR (epidermal growth factor receptor) signaling pathway is frequently deregulated in many malignancies. Therefore, targeting the EGFR pathway is regarded as a promising strategy for anticancer drug discovery. Herein, we identified a 2-amino-nicotinonitrile compound (w09) as a novel autophagy enhancer, which potently induced macroautophagy/autophagy and consequent apoptosis in gastric cancer cells. Mechanistic studies revealed that EGFR-mediated activation of the RAS-RAF1-MAP2K-MAPK1/3 signaling pathway played a critical role in w09-induced autophagy and apoptosis of gastric cancer cells. Inhibition of the MAPK1/3 pathway with U0126 or blockade of autophagy by specific chemical inhibitors markedly attenuated the effect of w09-mediated growth inhibition and caspase-dependent apoptosis. Furthermore, these conclusions were supported by knockdown of ATG5 or knockout of ATG5 and/or ATG7. Notably, w09 increased the expression of SQSTM1 by transcription, and knockout of SQSTM1 or deleting the LC3-interaction region domain of SQSTM1, significantly inhibited w09-induced PARP1 cleavage, suggesting the central role played by SQSTM1 in w09-induced apoptosis. In addition, in vivo administration of w09 effectively inhibited tumor growth of SGC-7901 xenografts. Hence, our findings not only suggested that activation of the EGFR-RAS-RAF1-MAP2K-MAPK1/3 signaling pathway may play a critical role in w09-induced autophagy and apoptosis, but also imply that induction of autophagic cancer cell death through activation of the EGFR pathway may be a potential therapeutic strategy for EGFR-disregulated gastric tumors.

Indexed as

ApoptosisMAP Kinase Signaling SystemAnimalsAntineoplastic AgentsAutophagyCaspasesCell Line, TumorErbB ReceptorsHumansMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase KinasesNitrilesProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)Antineoplastic AgentsCaspasesErbB ReceptorsMAPK1 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase KinasesNitrilesProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)PyridinesSequestosome-1 ProteinSQSTM1 protein, humanapoptosisATG7autophagyEGFRgastric cancerLC3lysosomeRAS-RAF1-MAP2K-MAPK1/3SQSTM1w09

Identifiers

PMID28513279
PMCPMC5529067
OpenAlexW2616379805

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.