Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA289001 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Single-cell analysis reveals a stem cell program in human metastatic breast cancer cells (Human patients - mammary cells)
| PRJNA289006 | ENA
Project description:Metastasis remains the major cause of mortality in triple-negative breast cancer (TNBC), yet the metastatic potential of primary tumors is difficult to predict at diagnosis. Here, we leveraged patient-derived xenograft (PDX) models as a functional readout of primary tumor metastatic propensity. We first performed integrated genomic and transcriptomic profiling of primary breast tumors and their matched PDX models and found that key driver mutations, recurrent copy number alterations, and molecular subtype features were largely conserved between patient tumors and xenografts. These findings support the utility of matched PDX models as clinically relevant platforms for studying tumor-intrinsic features associated with breast cancer progression. We next focused on TNBC PDX models with reproducible metastatic phenotypes across biological replicates and classified primary tumors into metastatic and non-metastatic groups based on their matched PDX behavior. Single-cell transcriptomic profiling of these tumors revealed that metastatic samples were characterized by hypoxia-associated metabolic reprogramming, with coordinated activation of hypoxia and glycolysis pathways. This metabolic phenotype was associated with poor clinical outcome in independent breast cancer cohorts. Network-based prioritization identified adenylate kinase 1 (AK1) as a candidate regulator of this metastatic program. Functionally, AK1 promoted metastatic potential in primary tumor by supporting glycolytic ATP production, resistance to hypoxic and oxidative stress, and promoting trans-endothelial migration. Together, our findings establish primary tumor–matched PDX models as a clinically relevant discovery platform for metastatic potential, overcoming the challenge that future metastatic events are not readily predictable from primary tumors at diagnosis. Using reproducible PDX metastasis as a functional readout, we identify AK1-mediated metabolic stress adaptation as a key mechanism underlying metastatic potential in primary TNBC.
2026-06-30 | GSE334033 | GEO
Project description:Metastasis remains the major cause of mortality in triple-negative breast cancer (TNBC), yet the metastatic potential of primary tumors is difficult to predict at diagnosis. Here, we leveraged patient-derived xenograft (PDX) models as a functional readout of primary tumor metastatic propensity. We first performed integrated genomic and transcriptomic profiling of primary breast tumors and their matched PDX models and found that key driver mutations, recurrent copy number alterations, and molecular subtype features were largely conserved between patient tumors and xenografts. These findings support the utility of matched PDX models as clinically relevant platforms for studying tumor-intrinsic features associated with breast cancer progression. We next focused on TNBC PDX models with reproducible metastatic phenotypes across biological replicates and classified primary tumors into metastatic and non-metastatic groups based on their matched PDX behavior. Single-cell transcriptomic profiling of these tumors revealed that metastatic samples were characterized by hypoxia-associated metabolic reprogramming, with coordinated activation of hypoxia and glycolysis pathways. This metabolic phenotype was associated with poor clinical outcome in independent breast cancer cohorts. Network-based prioritization identified adenylate kinase 1 (AK1) as a candidate regulator of this metastatic program. Functionally, AK1 promoted metastatic potential in primary tumor by supporting glycolytic ATP production, resistance to hypoxic and oxidative stress, and promoting trans-endothelial migration. Together, our findings establish primary tumor–matched PDX models as a clinically relevant discovery platform for metastatic potential, overcoming the challenge that future metastatic events are not readily predictable from primary tumors at diagnosis. Using reproducible PDX metastasis as a functional readout, we identify AK1-mediated metabolic stress adaptation as a key mechanism underlying metastatic potential in primary TNBC.
2026-06-30 | GSE336789 | GEO
Project description:Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here we establish a robust method for identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA-sequencing and patient-derived xenograft (PDX) models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity, but micrometastases harbor a distinct transcriptome program conserved across PDX models that is highly predictive of poor survival in patients. Pathway analysis revealed mitochondrial oxidative phosphorylation (OXPHOS) as the top pathway upregulated in micrometastases, in contrast to higher levels of glycolytic enzymes in primary tumour cells, which we corroborated by flow cytometric and metabolomic analyses. Pharmacological inhibition of OXPHOS dramatically attenuated metastatic seeding in the lungs, which demonstrates the functional importance of OXPHOS in seeding and highlights its potential as a therapeutic target to prevent metastatic spread in breast cancer patients.
2020-02-20 | GSE123837 | GEO
Project description:Local invasion is a critical early step in metastatic cancer. This study investigated the invasion mechanisms of primary (IGR39) and metastatic (IGR37) melanoma cells at the single-cell level using single-probe single-cell mass spectrometry (SCMS). We detected 166 of 228 metabolites in IGR39 and 168 of 172 in IGR37.
2025-08-12 | MSV000098805 | GNPS
Project description:Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44+ cancer cells metastasized to the liver than those at the primary site.
2020-12-22 | GSE151191 | GEO
Project description:Patients diagnosed with estrogen receptor (ER) positive breast cancer have a prolonged risk of distal metastatic recurrence to vital organs. Metastatic disease is incurable at present due to the development of treatment resistant cell populations. Here we used single-cell RNA sequencing to evaluate the transcriptome heterogeneity of ER+ breast cancer patient-derived xenografts (PDX) tropic for three common breast cancer metastatic sites – bone, brain, and liver – compared to primary tumors grown in the mammary fat pad. Metastatic cell populations at each location were phenotypically distinct from primary tumor cells with unique transcriptional programs indicative of signaling programs driven by specific transcription factors. Cells that metastasized to brain and liver tissue adopted gene expression programs indicative of the target organ microenvironments. Discerning the organ-specific phenotypic adaptations of metastatic ER+ breast cancer cells may help tailor appropriate therapies for individual patients and to each metastatic site.
2020-05-09 | GSE131007 | GEO
Project description:Metastatic cancer cells, originating from cancer stem cells with metastatic capacity, utilize nutrient flexibility to overcome the hurdles of metastatic cascade. However, the nutrient supply for maintaining the stemness potentials of metastatic cancer cells remains unknown. Here, we revealed that metastatic breast cancer cells maintain stemness and initiate metastasis upon detachment via uptaking and oxidating lactate. In detached metastasizing breast cancer cells, lactate was incorporated into tricarboxylic acid cycle and boosted oxidative phosphorylation, and then promoted the stemness potentials via α-KG-DNMT3B-mediated SOX2 hypomethylation. Moreover, lactate was uptake and oxidated in mitochondria by CD147/MCT1/LDHB complex, whose existence correlates to the stemness potentials and tumor metastasis in breast cancer patients. An intracellularly expressed single chain variable fragment targeting mitochondrial CD147 (mito-CD147 scFv) effectively disrupted mitochondrial CD147/MCT1/LDHB complex, inhibited lactate-induced stemness potentials, depleted circulating breast cancer cells and reduced metastatic burden, suggesting a promising clinical application in reducing lactate-fueled metastasis.
2025-01-09 | PXD059617 |
Project description:The omentum, a visceral adipose tissue with critical metabolic, immunological, and stem cell functions is the preferred site for ovarian cancer metastasis. However, its role in maintaining homeostasis and its responses to metastatic colonization remain incompletely understood. Using single-cell transcriptomics, we profiled different anatomical regions of the omentum in patients with benign conditions and ovarian cancer metastasis. We cataloged the benign omentum and found stable cell type composition and preservation of a stem and progenitor niche. Upon metastatic colonization, the immune landscape diversified accompanied by a gradual loss of mesothelial and progenitor cells. The lesser omentum, which is not routinely removed during surgical debulking, was identified as a premetastatic niche characterized by neutrophil infiltration, NETosis, and the presence of micrometastases. At established metastatic sites, resident cells exhibited cancer-associated phenotypes with regulatory, anti-adipogenic, and immunosuppressive functions. Cancer cells orchestrated the cell reprogramming via a repertoire of signaling factors affecting both proximal and distal omental tissue. This cell atlas illuminates the cellular and molecular determinants of organ homeostasis and reveals a high degree of plasticity and cellular reprogramming promoted by cancer colonization.
2024-11-07 | MSV000096327 | MassIVE