# NCEH1 promotes breast cancer progression by regulating NRP1 and activating the TNF-α/NF-κB signalling pathway

**Authors:** Jie Sun, Yaqian Liu, Jieji Mo, Jialin Zhou, Xue Bai, Boshi Gu, Jun Li, Haidong Zhao

PMC · DOI: 10.1080/19336918.2026.2616948 · 2026-01-27

## TL;DR

NCEH1 promotes breast cancer by regulating NRP1 and activating the TNF-α/NF-κB pathway, making it a potential new target for treatment.

## Contribution

NCEH1's role in breast cancer progression via NRP1 and TNF-α/NF-κB pathway activation is newly identified.

## Key findings

- NCEH1 expression is significantly higher in breast cancer tissues and cells.
- NCEH1 silencing reduces cancer cell proliferation and migration.
- NCEH1 promotes malignancy by regulating NRP1 and activating the TNF-α/NF-κB pathway.

## Abstract

Neutral cholesterol ester hydrolase 1 (NCEH1), a key enzyme in cellular lipid metabolism, is associated with cancer progression. Its molecular functions in breast cancer remain poorly understood.

This study evaluated the expression of NCEH1 in breast cancer patients using multiple databases. Functionally, the effects of NCEH1 silencing or overexpression on breast cancer cell growth and motility were investigated. RNA-seq was employed to identify downstream target genes and signalling pathways.

The expression of NCEH1 in breast cancer tissues and cells was significantly higher than that in normal tissues and cells. Silencing NCEH1 suppressed breast cancer cell proliferation and migration. Mechanistically, NCEH1 regulated Neuropilin-1 (NRP1) expression, and both promoted malignant phenotypes in breast cancer by activating the TNF-α/NF-κB signalling pathway.

Our findings demonstrate that NCEH1 accelerates breast cancer progression by modulating NRP1 and activating the TNF-α/NF-κB signalling pathway. Collectively, NCEH1 represents a potential novel biomarker and therapeutic target for breast cancer.

## Linked entities

- **Genes:** NCEH1 (neutral cholesterol ester hydrolase 1) [NCBI Gene 57552], NRP1 (neuropilin 1) [NCBI Gene 8829], TNF (tumor necrosis factor) [NCBI Gene 7124], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** SNAI2 (snail family transcriptional repressor 2) [NCBI Gene 6591] {aka SLUG, SLUGH, SLUGH1, SNAIL2, WS2D}, NRP1 (neuropilin 1) [NCBI Gene 8829] {aka BDCA4, CD304, NP1, NRP, VEGF165R}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, NCEH1 (neutral cholesterol ester hydrolase 1) [NCBI Gene 57552] {aka AADACL1, NCEH}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, AURKB (aurora kinase B) [NCBI Gene 9212] {aka AIK2, AIM-1, AIM1, ARK-2, ARK2, AurB}, LIPA (lipase A, lysosomal acid type) [NCBI Gene 3988] {aka CESD, LAL}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Nrp1 (neuropilin 1) [NCBI Gene 18186] {aka C530029I03, NP-1, NPN-1, Npn1, Nrp}, VIM (vimentin) [NCBI Gene 7431], PAX2 (paired box 2) [NCBI Gene 5076] {aka FSGS7, PAPRS, PAX-2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, LTA (lymphotoxin alpha) [NCBI Gene 4049] {aka LT, TNFB, TNFSF1, TNLG1E}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Nceh1 (neutral cholesterol ester hydrolase 1) [NCBI Gene 320024] {aka Aadacl1, B230106I24Rik, CPO-BP, Nceh}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}
- **Diseases:** prostate cancer (MESH:D011471), cholangiocarcinoma (MESH:D018281), lung metastasis (MESH:D009362), cervical cancer (MESH:D002583), lung adenocarcinoma (MESH:D000077192), TNBC (MESH:D064726), Breast cancer (MESH:D001943), inflammatory (MESH:D007249), axillary lymph node metastasis (MESH:D008207), carcinogenic (MESH:D011230), pancreatic cancer (MESH:D010190), non-small cell lung cancer (MESH:D002289), glioblastoma (MESH:D005909), melanoma (MESH:D008545), lung cancer (MESH:D008175), triple (MESH:C536008), liver cancer (MESH:D006528), MDD (MESH:D003865), ovarian cancer (MESH:D010051), Cancer (MESH:D009369), gastric cancer (MESH:D013274), head and neck cancer (MESH:D006258)
- **Chemicals:** EDTA (MESH:D004492), ethanol (MESH:D000431), propidium iodide (MESH:D011419), streptomycin (MESH:D013307), penicillin (MESH:D010406), TritonX-100 (MESH:D017830), paraformaldehyde (MESH:C003043), H&amp;E (MESH:D006371), reactive oxygen species (MESH:D017382), eosin (MESH:D004801), crystal violet (MESH:D005840), Cholesterol (MESH:D002784), Hematoxylin (MESH:D006416), CO2 (MESH:D002245), Paraffin (MESH:D010232), Lipofectamine 2000 (MESH:C086724), gemcitabine (MESH:D000093542), SDS (MESH:D012967), polybrene (MESH:D006583), formalin (MESH:D005557), TRIzol (MESH:C411644), lipid (MESH:D008055), PEI (MESH:D011094), PI (MESH:D010716), balsam (MESH:D001453), cholesterol esters (MESH:D002788), DAPI (MESH:C007293), methanol (MESH:D000432), BCA (MESH:C047117), 2-acetylmonoalkyl glycerol ether (-), puromycin (MESH:D011691)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** SK-BR3 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0033), MDA-MB-453 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0418), MCF-10A — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), HCC1954 — Homo sapiens (Human), Breast ductal carcinoma, Cancer cell line (CVCL_1259), MB-MDA-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), HCC1806 — Homo sapiens (Human), Breast acantholytic squamous cell carcinoma, Cancer cell line (CVCL_1258), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12851389/full.md

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Source: https://tomesphere.com/paper/PMC12851389