Evidence map›Paper›PMID 32027103›Full record

ArticleFEBS open bio2020

The PI3K/mTOR dual inhibitor NVP-BEZ235 stimulates mutant p53 degradation to exert anti-tumor effects on triple-negative breast cancer cells.

Jiajing Cai, Jingruo Xia, Jiang Zou, Qiang Wang, Qiang Ma, Ru Sun, Hebin Liao, Lei Xu, Dongsheng Wang, Xiaolan Guo

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in FEBS open bio, 2020. 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 It has been retracted, and should not be counted.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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 29 citations in OpenAlex.

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  19. Targeting Autophagy in Breast Cancer.International journal of molecular sciences · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Jiajing CaiDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.ORCID 0000-0001-6731-8003
Jingruo XiaDepartment of Laboratory Medicine, North Sichuan Medical College, Nanchong, China.
Jiang ZouDepartment of Laboratory Medicine, North Sichuan Medical College, Nanchong, China.
Qiang WangDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Qiang MaDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Ru SunDepartment of Laboratory Medicine, North Sichuan Medical College, Nanchong, China.
Hebin LiaoTranslational Medicine Research Center, North Sichuan Medical College, Nanchong, China.
Lei XuTranslational Medicine Research Center, North Sichuan Medical College, Nanchong, China.
Dongsheng WangDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Xiaolan GuoDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
North Sichuan Medical University · CNAffiliated Hospital of North Sichuan Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nearly half of human cancers harbor p53 mutations, and mutant p53 (mutp53) promotes carcinogenesis, metastasis, tumor recurrence and chemoresistance. mutp53 is observed in 30% of breast carcinomas, including triple-negative breast cancer (TNBC), and thus mutp53 is a promising target for treatment of TNBC. In this study, we investigated the effect of a phosphatidylinositide 3 kinase/mammalian target of rapamycin dual inhibitor, NVP-BEZ235 (BEZ235), on two TNBC cell lines with mutp53: MDA-MB-231 and MDA-MB-468. Cell growth, migration and colony-formation abilities were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, scratch assay, transwell and soft agar assay, revealing that BEZ235 can inhibit the growth, migration and colony-formation abilities of TNBC cells. In addition, BEZ235 caused degradation of mutp53 in these cells. We investigated the underlying mechanism by inhibiting proteasome function using MG132 and inhibiting autophagy using 3-methyladenine and shRNAs. We observed that BEZ235 may induce autophagy through repression of the Akt/mammalian target of rapamycin signaling pathway. The observed interplay between mutp53 and autophagy in TNBC cells was examined further by knockdown of ATG5 and ATG7, revealing that degradation of mutp53 induced by BEZ235 may be independent of the ubiquitin-proteasome pathway and autophagy mediated by ATG5 and ATG7. Moreover, we found evidence of positive feedback between mutp53 and autophagy in TNBC cells. In conclusion, BEZ235 may exert antitumor effects against TNBC cells by targeting mutp53, and this may have implications for the development of future therapies.

Indexed as

Antineoplastic AgentsAutophagyCell Line, TumorCell MovementCell ProliferationCell SurvivalFemaleHumansImidazolesMutant ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProteolysisProto-Oncogene Proteins c-aktQuinolinesSignal TransductionAntineoplastic AgentsdactolisibImidazolesMTOR protein, humanMutant ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktQuinolinesTOR Serine-Threonine KinasesTP53 protein, humanTumor Suppressor Protein p53autophagymechanistic target of rapamycin signal transduction pathwaymutant p53NVP-BEZ235protein kinase Btriple-negative breast cancer

Identifiers

PMID32027103
PMCPMC7137801
OpenAlexW3004924135

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.