Evidence map›Paper›PMID 35115500›Full record

ArticleCell death & disease2022

DGKZ promotes TGFβ signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGFβR2.

Yuanyuan Zhao, Hefen Sun, Xuan Li, Qiqi Liu, Yang Liu, Yifeng Hou, Wei Jin

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Macrophage DGKActa pharmaceutica Sinica. B · 2025
    Article
  4. Article
  5. 3Oncology research · 2025
    Article
  6. Review
  7. Review
  8. miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFβR2.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  9. Review
  10. Article
  11. Article
  12. Article
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

7 authors at 2 institutions in 1 country.

Yuanyuan Zhao *Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.ORCID 0000-0001-7700-9968
Hefen Sun *Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. sunhefen2006@163.com.ORCID 0000-0002-8201-5112
Xuan LiDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.ORCID 0000-0003-2851-8963
Qiqi LiuDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.ORCID 0000-0001-9032-4858
Yang LiuDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.ORCID 0000-0003-0820-0683
Yifeng HouDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.ORCID 0000-0003-2262-1919
Wei JinDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. jinwei@fudan.edu.cn.ORCID 0000-0001-8263-571X
Shanghai Medical College of Fudan University · CNFudan University Shanghai Cancer Center · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81972727
6 · The paper itself

Abstract

Diacylglycerol kinase ζ (DGKZ) is a diacylglycerol kinase that metabolizes diacylglycerol to yield phosphatidic acid, and its function in breast cancer progression remains unclear. In this study, via screening of a CRISPR-Cas9 knockout library containing lipid metabolic genes, DGKZ was identified as a potential prometastatic gene. We first confirmed that high DGKZ expression correlated with tumor progression and poor prognosis in patients. Next, knockout of DGKZ in triple-negative breast cancer cell lines were found to significantly inhibit metastatic behaviors in vitro and in vivo, whereas its overexpression increased the metastatic potential of cell lines. Mechanistic studies based on RNA sequencing and bioinformatic analysis indicated that DGKZ might regulate cell metastasis by promoting epithelial-mesenchymal transition via the transforming growth factor β (TGFβ) signaling pathway. Furthermore, we found that overexpression of DGKZ activated the TGFβ/TGFβR2/Smad3 signaling pathway by inhibiting the degradation of TGFβR2 through suppression of caveolin/lipid raft-dependent endocytosis. Moreover, the caveolin/lipid raft-dependent endocytosis of TGFβR2 was regulated by the metabolite phosphatidic acid, which might alter TGFβR2 partitioning in lipid rafts and nonlipid rafts by affecting the fluidity of the plasma membrane. These findings suggested that DGKZ is a novel promoter of metastasis and that it could be a potential prognostic indicator in patients with triple-negative breast cancer.

Indexed as

Diacylglycerol KinaseTriple Negative Breast NeoplasmsCaveolinsCell Line, TumorCell ProliferationEndocytosisHumansMembrane MicrodomainsPhosphatidic AcidsReceptor, Transforming Growth Factor-beta Type IISignal TransductionTransforming Growth Factor betaCaveolinsDGKZ protein, humanDiacylglycerol KinasePhosphatidic AcidsReceptor, Transforming Growth Factor-beta Type IITGFBR2 protein, humanTransforming Growth Factor beta

Identifiers

PMID35115500
PMCPMC8814002
OpenAlexW4210368414

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.