Evidence map›Paper›PMID 30817646›Full record

ArticlePlastic and reconstructive surgery2019

CRISPR/Cas9-Mediated BRCA1 Knockdown Adipose Stem Cells Promote Breast Cancer Progression.

Ruya Zhao, Rayan Kaakati, Xinjian Liu, Lingfan Xu, Andrew K Lee, Robin Bachelder, Chuan-Yuan Li, Scott T Hollenbeck

Abstract read
In one paragraph

Article in Plastic and reconstructive surgery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Article
  2. Review
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  4. Article
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  9. Review
  10. Review
  11. Article
  12. Review
  13. CRISPR/Cas9-Mediated Genome Editing in Cancer Therapy.International journal of molecular sciences · 2023
    Review
  14. Review
  15. Review
  16. Review
  17. Cancers · 2021
    Review
  18. Article
  19. Article
  20. The Role ofCancers · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Ruya ZhaoFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Rayan KaakatiFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Xinjian LiuFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Lingfan XuFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Andrew K LeeFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Robin BachelderFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Chuan-Yuan LiFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.
Scott T HollenbeckFrom Duke University School of Medicine, the Departments of Dermatology and Pathology, and the Division of Plastic and Reconstructive Surgery, Duke University.

Funding

Targeting apoptotic caspases to enhance cancer radiotherapyR01CA216876 · NCI · DUKE UNIVERSITY · PI LI, FANG · 2018 to 2022
$2.3M
Necroptotic genes in cancer cellular response to radiationR01CA208852 · NCI · DUKE UNIVERSITY · PI LI, FANG · 2017 to 2021
$2.2M
Pro-oncogenic roles of apoptotic caspasesR01ES024015 · NIEHS · DUKE UNIVERSITY · PI LI, CHUAN-YUAN · 2014 to 2018
$1.8M
NCI NIH HHS R01 CA208852NCI NIH HHS R01 CA216876NIEHS NIH HHS R01 ES024015
6 · The paper itself

Abstract

backgroundThe tumor microenvironment within the breast is rich in adipose elements. The interaction between adipose cells and breast cancer is poorly understood, particularly as it pertains to patients with genetic susceptibility to breast cancer. This study focuses on the phenotype of human adipose-derived stem cells with the BRCA1 mutation and the effect they may have on breast cancer cell behavior.

methodsCRISPR/Cas9 was used to generate de novo BRCA1-knockdown human adipose-derived stem cells. The effect of the BRCA1 knockdown on the adipose-derived stem cell phenotype was compared to wild-type adipose-derived stem cells and patient-derived breast adipose-derived stem cells with known BRCA1 mutations. Interactions between adipose-derived stem cells and the MDA-MB-231 breast cancer cell line were evaluated.

resultsBRCA1-knockdown adipose-derived stem cells stimulated MDA-MB-231 proliferation (1.4-fold increase on day 4; p = 0.0074) and invasion (2.3-fold increase on day 2; p = 0.0171) compared to wild-type cells. Immunofluorescence staining revealed higher levels of phosphorylated ataxia telangiectasia-mutated activation in BRCA1-knockdown cells (72.9 ± 5.32 percent versus 42.9 ± 4.97 percent; p = 0.0147), indicating higher levels of DNA damage. Beta-galactosidase staining demonstrated a significantly higher level of senescence in BRCA1-knockdown cells compared with wild-type cells (7.9 ± 0.25 percent versus 0.17 ± 0.17 percent; p < 0.0001). Using quantitative enzyme-linked immunosorbent assay to evaluate conditioned media, the authors found significantly higher levels of interleukin-8 in BRCA1-knockdown cells (2.57 ± 0.32-fold; p = 0.0049).

conclusionsThe authors show for the first time that the BRCA1 mutation affects the adipose-derived stem cell phenotype. Moreover, CRISPR/Cas9-generated BRCA1-knockdown adipose-derived stem cells stimulate a more aggressive behavior in breast cancer cells than wild-type adipose-derived stem cells. This appears to be related to increased inflammatory cytokine production by means of a DNA damage-mediated cell senescence pathway.

Indexed as

Adipose TissueAdultBRCA1 ProteinBreast NeoplasmsCell LineCell Transformation, NeoplasticCRISPR-Cas SystemsCulture Media, ConditionedDisease ProgressionFemaleGene Knockdown TechniquesHumansInterleukin-8Middle AgedPrimary Cell CultureStem CellsBRCA1 ProteinBRCA1 protein, humanCulture Media, ConditionedCXCL8 protein, humanInterleukin-8

Identifiers

PMID30817646
PMCPMC6400326

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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.