Evidence map›Paper›PMID 25375375›Full record

ArticleCell death & disease2014

Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation.

C Kao, A Chao, C-L Tsai, W-C Chuang, W-P Huang, G-C Chen, C-Y Lin, T-H Wang, H-S Wang, C-H Lai

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
6.2field-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

68 citing papers in PubMed, 116 citations in OpenAlex.

  1. Review
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  16. Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Article
  19. In utero hypoxia attenuated acetylcholine-mediated vasodilatation via CHRM3/p-NOS3 in fetal sheep MCA: role of ROS/ERK1/2.Hypertension research : official journal of the Japanese Society of Hypertension · 2022
    Article
  20. The Multifaceted Role of Autophagy in Endometrium Homeostasis and Disease.Reproductive sciences (Thousand Oaks, Calif.) · 2022
    Review

8 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

10 authors at 4 institutions in 1 country.

C Kao1] Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
A ChaoDepartment of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
C-L TsaiDepartment of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
W-C Chuang1] Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
W-P HuangDepartment of Life Science, National Taiwan University, Taipei, Taiwan.
G-C ChenInstitute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
C-Y LinDepartment of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
T-H Wang1] Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan [3] Genomic Medicine Research Core Laboratory, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan [4] School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
H-S Wang1] Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
C-H LaiDepartment of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Chang Gung Memorial Hospital · TWChang Gung University · TWInstitute of Biological Chemistry, Academia Sinica · TWNational Taiwan University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The antitumor activity of an inhibitor of 26S proteasome bortezomib (Velcade) has been observed in various malignancies, including colon cancer, prostate cancer, breast cancer, and ovarian cancer. Bortezomib has been proposed to stimulate autophagy, but scientific observations did not always support this. Interactions between ERK activity and autophagy are complex and not completely clear. Autophagy proteins have recently been shown to regulate the functions of ERK, and ERK activation has been found to induce autophagy. On the other hand, sustained activation of ERK has also been shown to inhibit the maturation step of the autophagy process. In this study, we sought to identify the mechanism of autophagy regulation in cancer cells treated with bortezomib. Our results indicate that bortezomib blocked the autophagic flux without inhibiting the fusion of the autophagosome and lysosome. In ovarian cancer, as well as endometrial cancer and hepatocellular carcinoma cells, bortezomib inhibited protein degradation in lysosomes by suppressing cathepsins, which requires the participation of ERK phosphorylation, but not JNK or p38. Our findings that ERK phosphorylation reduced cathepsins further explain how ERK phosphorylation inhibits the autophagic flux. In conclusion, bortezomib may induce ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors. The inhibition of cisplatin-induced autophagy by bortezomib can enhance chemotherapy efficacy in ovarian cancer. As we also found that bortezomib blocks the autophagic flux in other cancers, the synergistic cytotoxic effect of bortezomib by abolishing chemotherapy-related autophagy may help us develop strategies of combination therapies for multiple cancers.

Indexed as

Gene Expression Regulation, NeoplasticAntineoplastic AgentsAutophagyBoronic AcidsBortezomibCell Line, TumorCell SurvivalCisplatinExtracellular Signal-Regulated MAP KinasesFemaleHumansLeupeptinsMAP Kinase Kinase 4Ovarian Neoplasmsp38 Mitogen-Activated Protein KinasesPhagosomesAntineoplastic Agentsbenzyloxycarbonylleucyl-leucyl-leucine aldehydeBoronic AcidsBortezomibCisplatinExtracellular Signal-Regulated MAP KinasesLeupeptinsMAP Kinase Kinase 4p38 Mitogen-Activated Protein KinasesProteasome InhibitorsPyrazines

Identifiers

PMID25375375
PMCPMC4260726
OpenAlexW2053144360

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.