ArticleProceedings of the National Academy of Sciences of the United States of America2017
CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- NR4A Family Genes: A Review of Comprehensive Prognostic and Gene Expression Profile Analysis in Breast Cancer.Frontiers in oncology · 2022Pooled it
- Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer.The Journal of clinical investigation · 2018Trial
- Population-Associated Molecular Variation in Histologically Normal Breast Tissue Is Associated with Distinct Baseline Transcriptional States.International journal of molecular sciences · 2026Article
- CD6-Directed Immunotherapy Targets Breast Cancer Stem Cell Function and Enhances Immune-Mediated Cytotoxicity in Triple-Negative Breast Cancer.Biomolecules · 2026Article
- TFF1-mediated suppression of the TCA cycle promotes bone metastasis in triple-negative breast cancer.Translational oncology · 2026Article
- PLIN2-PGAM5-regulated lipid droplet-mitochondria contacts drive microglial neuroinflammation after spinal cord injury via fatty acid metabolic reprogramming.Cell death and differentiation · 2026Article
- SIRT7-mediated ACSL3 delactylation suppresses colorectal cancer progression by orchestrating tumor-associated macrophage ferroptosis and polarization.Cell death & disease · 2026Article
- Multiomic and functional validation of ACSL3, a regulator of fatty acid metabolism, as a lymph node metastasis-associated gene in lung adenocarcinoma.Respiratory research · 2026Article
- ACSL5 Mediates Adaptation to the Palmitic Acid-Enriched Pulmonary Microenvironment to Enhance Metastatic Breast Cancer Cell Survival and Lung Metastasis.Cancer research · 2026Article
- The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling.Clinical and translational medicine · 2026Review
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- In vivo imaging of metabolic heterogeneity across three endpoints relevant to aggressive breast cancer.PNAS nexus · 2026Article
- Emerging roles and therapeutic implications of lipid droplet protein perilipin 2 in liver disease.Genes & diseases · 2026Review
- Mortality differences in coronary patients with breast cancer treated with trimetazidine dihydrochloride: potential therapeutic implications.Cardio-oncology (London, England) · 2025Article
- CDCP1 allosterically regulates the AMPK α1 subunit to enhance fatty acid oxidation in osteoblasts.Cellular & molecular biology letters · 2025Article
- TMEM166 negatively regulates unfolded protein response to affect hepatocellular carcinoma cell growth and sorafenib resistance.Cell death & disease · 2025Article
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Lipid droplet dynamics in type 2 diabetes and its complications: pathophysiological insights and therapeutic options.Lipids in health and disease · 2025Review
- CDCP1-targeting ADC outperforms standard therapies in Ras-mutant pancreatic cancer.Molecular therapy. Oncology · 2025Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) is notoriously aggressive with high metastatic potential, which has recently been linked to high rates of fatty acid oxidation (FAO). Here we report the mechanism of lipid metabolism dysregulation in TNBC through the prometastatic protein, CUB-domain containing protein 1 (CDCP1). We show that a "low-lipid" phenotype is characteristic of breast cancer cells compared with normal breast epithelial cells and negatively correlates with invasiveness in 3D culture. Using coherent anti-Stokes Raman scattering and two-photon excited fluorescence microscopy, we show that CDCP1 depletes lipids from cytoplasmic lipid droplets (LDs) through reduced acyl-CoA production and increased lipid utilization in the mitochondria through FAO, fueling oxidative phosphorylation. These findings are supported by CDCP1's interaction with and inhibition of acyl CoA-synthetase ligase (ACSL) activity. Importantly, CDCP1 knockdown increases LD abundance and reduces TNBC 2D migration in vitro, which can be partially rescued by the ACSL inhibitor, Triacsin C. Furthermore, CDCP1 knockdown reduced 3D invasion, which can be rescued by ACSL3 co-knockdown. In vivo, inhibiting CDCP1 activity with an engineered blocking fragment (extracellular portion of cleaved CDCP1) lead to increased LD abundance in primary tumors, decreased metastasis, and increased ACSL activity in two animal models of TNBC. Finally, TNBC lung metastases have lower LD abundance than their corresponding primary tumors, indicating that LD abundance in primary tumor might serve as a prognostic marker for metastatic potential. Our studies have important implications for the development of TNBC therapeutics to specifically block CDCP1-driven FAO and oxidative phosphorylation, which contribute to TNBC migration and metastasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.