Evidence map›Paper›PMID 19376776›Full record

ArticleThe Journal of biological chemistry2009

Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression.

Chunmei Wang, Runzi Qi, Nan Li, Zhengxin Wang, Huazhang An, Qinghua Zhang, Yizhi Yu, Xuetao Cao

RetractedOpen access · hybridAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 89 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Chunmei WangFrom the National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Runzi QiFrom the National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Nan LiFrom the National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Zhengxin WangDepartment of Surgery, Changzheng Hospital, Shanghai 200003, China.
Huazhang AnDepartment of Surgery, Changzheng Hospital, Shanghai 200003, China.
Qinghua ZhangDepartment of Surgery, Changzheng Hospital, Shanghai 200003, China.
Yizhi YuDepartment of Surgery, Changzheng Hospital, Shanghai 200003, China. Electronic address: cjcb@sh163.net.
Xuetao CaoFrom the National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China. Electronic address: caoxt@public3.sta.net.cn.
Second Military Medical University · CNShanghai Changzheng Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Notch signaling plays a critical role in regulating cell proliferation, differentiation, and apoptosis. Our previous study showed that overexpression of Notch1 could inhibit human hepatocellular carcinoma (HCC) cell growth by arresting the cell cycle and inducing apoptosis. HCC cells are resistant to apoptotic induction by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), so new therapeutic approaches have been explored to sensitize HCC cells to TRAIL-induced apoptosis. We are wondering whether and how Notch1 signaling can enhance the sensitivity of HCC cells to TRAIL-induced apoptosis. In this study, we found that overexpression of ICN, the constitutive activated form of Notch1, up-regulated p53 protein expression in HCC cells by inhibiting proteasome degradation. p53 up-regulation was further observed in human primary hepatocellular carcinoma cells after activation of Notch signaling. Inhibition of the Akt/Hdm2 pathway by Notch1 signaling was responsible for the suppression of p53 proteasomal degradation, thus contributing to the Notch1 signaling-mediated up-regulation of p53 expression. Accordingly, Notch1 signaling could make HCC cells more sensitive to TRAIL-induced apoptosis, whereas Notch1 signaling lost the synergistic promotion of TRAIL-induced apoptosis in p53-silenced HepG2 HCC cells and p53-defective Hep3B HCC cells. The data suggest that enhancement of TRAIL-induced apoptosis by Notch1 signaling is dependent upon p53 up-regulation. Furthermore, Notch1 signaling could enhance DR5 expression in a p53-dependent manner. Taken together, Notch1 signaling sensitizes TRAIL-induced apoptosis in HCC cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression. Thus, our results suggest that activation of Notch1 signaling may be a promising approach to improve the therapeutic efficacy of TRAIL-resistant HCC.

Indexed as

ApoptosisCarcinoma, HepatocellularCell Line, TumorHumansLiver NeoplasmsProteasome Endopeptidase ComplexProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mdm2Receptor, Notch1Receptors, TNF-Related Apoptosis-Inducing LigandRNA, Small InterferingSignal TransductionTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alphaTumor Suppressor Protein p53Up-RegulationMDM2 protein, humanNOTCH1 protein, humanProteasome Endopeptidase ComplexProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mdm2Receptor, Notch1Receptors, TNF-Related Apoptosis-Inducing LigandRNA, Small InterferingTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanTumor Necrosis Factor-alphaTumor Suppressor Protein p53

Identifiers

PMID19376776
PMCPMC2713568
OpenAlexW2030887551

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.