Evidence map›Paper›PMID 31119045›Full record

ArticleCancer biology & medicine2019

The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility.

Fengjiao Jin, Zhaozhen Wu, Xiao Hu, Jiahui Zhang, Zihe Gao, Xiao Han, Junfang Qin, Chen Li, Yue Wang

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

Article in Cancer biology & medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
5.6field-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

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.

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  8. The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
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17 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

9 authors at 2 institutions in 1 country.

Fengjiao JinSchool of Medicine, Nankai University, Tianjin 300071, China.
Zhaozhen WuSchool of Medicine, Nankai University, Tianjin 300071, China.
Xiao HuSchool of Medicine, Nankai University, Tianjin 300071, China.
Jiahui ZhangSchool of Medicine, Nankai University, Tianjin 300071, China.
Zihe GaoSchool of Medicine, Nankai University, Tianjin 300071, China.
Xiao HanSchool of Medicine, Nankai University, Tianjin 300071, China.
Junfang QinSchool of Medicine, Nankai University, Tianjin 300071, China.
Chen LiInstitute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
Yue WangSchool of Medicine, Nankai University, Tianjin 300071, China.
Nankai University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo examine the effect of pSer9-GSK-3β on breast cancer and to determine whether the underlying metabolic and immunological mechanism is associated with ROS/eIF2B and natural killer (NK) cells.

methodsWe employed TWS119 to inactivate GSK-3β by phosphorylating Ser9 and explored its effect on breast cancer and NK cells. The expression of GSK-3β, natural killer group 2 member D (NKG2D) ligands, eIF2B was quantified by PCR and Western blot. We measured intracellular reactive oxygen species (ROS) and mitochondrial ROS using DCFH-DA and MitoSOX

resultsOur investigation revealed that TWS119 downregulated NKG2D ligands (H60a and Rae1), suppressed the cytotoxicity of NK cells, and promoted the migration of 4T1 murine breast cancer cells. Nevertheless, LY290042, which attenuates p-GSK-3β formation by inhibiting the PI3K/Akt pathway, reversed these effects. We also found that higher expression of pSer9-GSK-3β induced higher levels of ROS, and observed that abnormality of mitochondrial respiratory chain complex I/III function induced the dysfunction of GSK-3β-induced electron transport chain, naturally disturbing the ROS level. In addition, the expression of NOX3 and NOX4 was significantly up-regulated, which affected the generation of ROS and associated with the metastasis of breast cancer. Furthermore, we found that the expression of pSer535-eIF2B promoted the expression of NKG2D ligands (Mult-1 and Rae1) following by expression of pSer9-GSK-3β and generation of ROS.

conclusionsThe PI3K/Akt/GSK-3β/ROS/eIF2B pathway could regulate NK cell activity and sensitivity of tumor cells to NK cells, which resulted in breast cancer growth and lung metastasis. Thus, GSK-3β is a promising target of anti-tumor therapy.

Indexed as

breast cancereIF2BGSK-3βNK cellsNKG2D/NKG2DLsROS

Identifiers

PMID31119045
PMCPMC6528454
OpenAlexW2925318031

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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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.