Evidence map›Paper›PMID 33864166›Full record

ArticleBreast cancer research and treatment2021

NSDHL promotes triple-negative breast cancer metastasis through the TGFβ signaling pathway and cholesterol biosynthesis.

Mengting Chen, Yang Zhao, Xueli Yang, Yuanyuan Zhao, Qiqi Liu, Yang Liu, Yifeng Hou, Hefen Sun, Wei Jin

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Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.3field-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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  6. Article
  7. Breast Cancer Progression by the FGF/FGFR Axis: A Metabolic Perspective.Journal of mammary gland biology and neoplasia · 2025
    Review
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  19. Article
  20. Proactive and reactive roles of TGF-β in cancer.Seminars in cancer biology · 2023
    Review
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.

Mengting ChenKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Yang ZhaoKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Xueli YangKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Yuanyuan ZhaoKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Qiqi LiuKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Yang LiuKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Yifeng HouKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.
Hefen SunKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China. sunhefen2006@163.com.
Wei JinKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China. jinwei7207@163.com.ORCID http://orcid.org/0000-0001-8263-571X
Shanghai Medical College of Fudan University · CNFudan University Shanghai Cancer Center · CN

Funding

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

Abstract

purposeMetastasis is the main cause of breast cancer mortality. Recent studies have proved that lipid metabolic reprogramming plays critical roles in breast cancer carcinogenesis and metastasis. We aim to identify critical lipid metabolism genes in breast cancer metastasis.

methodsWe designed and cloned a CRISPR pooled library containing lipid metabolic gene guide RNAs and performed a genetic screen in vivo. Transwell assay and animal experiments were used to evaluate cell metastatic ability in vitro or in vivo, respectively. We performed immunohistochemistry with breast cancer tissue microarray to study the clinical significance of NSDHL.

findingsWe identified a cholesterol metabolic enzyme, NSDHL, as a potential metastatic driver in triple-negative breast cancer. NSDHL was highly expressed in breast cancer tissues and predicted a poor prognosis. NSDHL knockdown significantly suppressed cell proliferation and migration. Mechanistically, NSDHL activated the TGFβ signaling pathway by inhibiting the endosomal degradation of TGFβR2. In addition, blocking the upstream metabolism of NSDHL with ketoconazole rescued cancer metastasis and TGFβR2 degradation. However, the inactivation of NSDHL (Y151X) did not rescue the migration ability and the TGFβR2 protein expression.

conclusionTaken together, our findings established that NSDHL serves as a metastatic driver, and its function depends on its enzyme activity in cholesterol biosynthesis and is mediated by the NSDHL-TGFβR2 signal pathway. Our study indicated that NSDHL and steroid biosynthesis may serve as new drug targets for patients with advanced breast cancer.

Indexed as

3-Hydroxysteroid DehydrogenasesBreast NeoplasmsTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationCholesterolFemaleHumansNeoplasm MetastasisSignal TransductionTransforming Growth Factor beta3-Hydroxysteroid DehydrogenasesCholesterolNsdhl protein, humanTransforming Growth Factor betaBreast cancerCholesterol metabolismMetastasisTGFβ signaling pathway

Identifiers

PMID33864166
OpenAlexW3153686217

What OpenQuestion holds

Textmetadata
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.