Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA359116 | ENA |
REPOSITORIES: ENA
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Project description:Metastasis in triple-negative breast cancer
| PRJNA437929 | ENA
Project description:Triple-negative breast cancer is characterized by absence of oestrogen receptor, progesterone receptor, and a lack of HER2 amplification and is associated with poor patient prognosis and high rates of distant metastasis. These patients are at elevated risk of brain metastasis, which remains a major therapeutic challenge. IL13RA2, a high-affinity receptor for IL13, is highly expressed in primary brain cancers, many extracranial solid tumours, and in lung- and brain-seeking metastatic variant cell lines. However, the relationship between IL13RA2 and patient prognosis is variable, and the biological function of this receptor in cancer remains controversial. We sought to define the role of IL13RA2 in TNBC growth and metastasis, with an emphasis on breast-to-brain metastasis. We identified a positive correlation between elevated IL13RA2 mRNA expression and overall survival in a publicly available dataset of basal-like breast cancer patients. We generated IL13RA2-CRISPR knockout derivatives of the human brain-seeking breast cancer cell line MDA231BrM2 as well as murine 4T1 cells and evaluated changes in gene expression, proliferation, survival, and metastatic growth in vivo. We find that both IL13RA2-deficient models demonstrate enhanced survival and proliferation in vitro, as well as augmented metastatic tumour growth and worsened survival in intracardiac models of brain metastasis. Mechanistically, we observe increased AKT and NF-κB signalling in IL13RA2-deficient cells, which renders these cells highly sensitive to inhibition of AKT. We conclude that, in triple negative breast cancer, loss of IL13RA2 in tumour cells is strongly pro-metastatic, antiapoptotic, and pro-proliferative. These phenotypes are mediated through the AKT and NF-κB pathways. IL13RA2-deficient cells are highly vulnerable to AKT inhibition, which may represent a clinically useful vulnerability for patients with IL13RA2-low tumours. However, our data suggest that inhibition of IL13RA2, though promising in other tumour contexts, may be deleterious in metastatic triple-negative breast cancer.
2025-02-24 | GSE290037 | GEO
Project description:Targeted therapies for triple-negative breast cancer have increased the number of available treatment options for patients. However, an optimal treatment strategy is still an unmet medical need due to the lack of targetable biomarkers and tumour heterogeneity. Aptamers have high selectivity and specificity towards target proteins. Lower molecular weight, increased stability, less immunogenicity, and rapid tissue uptake make aptamers an attractive alternative to antibodies. Attempts to develop aptamer therapeutics have shown difficulties translating in vitro results to in vivo. Aptamer GreenB1 exhibits selectivity to triple-negative MDA-MB-231 human breast cancer cell line in vitro compared to estrogen, progesterone, and glucocorticoid receptor-expressing MCF-7 human breast cancer cell line. The aptamer is rapidly internalised into cells and trafficked to lysosomes. Here, we identify 1-integrin as the target protein for GreenB1 using proximity labelling and mass spectrometry proteomics. GreenB1 homes preferentially to the tumour in the 4T1 triple-negative breast cancer mice model in vivo.
2023-08-24 | PXD034982 | Pride
Project description:Triple therapy reduced metastasis in triple-negative breast cancer.
| PRJNA832953 | ENA
Project description:Molecular characteristics and metastasis predictor genes of triple-negative breast cancer
| PRJNA148225 | ENA
Project description:Plasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, triple-negative is the subtype that lacks the expression of major differentiation markers (i.e. estrogen receptor [ER]), ant its high cellular plasticity results in higher aggressiveness and poor prognosis compared to other subtypes. Whether plasticity poses a vulnerability to cancer cells remains elusive. Here, we show that cancer cell plasticity can be exploited to differentiate triple-negative breast cancer. Using a high-throughput reporter drug screen with 9,501 compounds, we identify three polo-like kinase 1 (PLK1) inhibitors as major inducers of ER protein expression and downstream activity in triple-negative breast cancer cells via the transcription factor BATF. PLK1 inhibition upregulates a cell differentiation program characterized by increased DNA damage, mitotic arrest and ultimately cell death. Notably, cells surviving PLK1 inhibition have decreased tumorigenic potential, and targeting PLK1 in already established tumours reduces tumour growth both in cell line and patient-derived xenograft models. In addition, genes upregulated upon PLK1 inhibition are correlated with expression in normal breast tissue and confer better overall survival in breast cancer patients. Our results indicate that differentiation therapy based on PLK1 inhibition might be an alternative strategy to treat triple-negative breast cancer.
2022-08-23 | PXD028495 | Pride
Project description:RNA-Seq was used to profile the transcriptomes of 63 breast cancer patient tumour samples (51 x ER+, 12 x triple negative) collected from the Utah Breast Cancer Study (UBCS).
2016-10-01 | E-MTAB-4993 | biostudies-arrayexpress
Project description:Molecular characteristics and metastasis predictor genes of triple-negative breast cancer (II)
| PRJNA232811 | ENA
Project description:Breast cancer is a heterogeneous disease classified into 3 major subtypes based on the presence or absence of molecular markers for oestrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor-2 (Her2) . Hormone receptor-positive BC (ER+, PR+ and Her-2-), accounts for approximately 70% of patients. Patients with ER- BC account for approximately 30 % of all cases and commonly have a worse prognosis than ER+ patients (9). However, a significant proportion of ER- cases have good outcomes and could potentially benefit from a less aggressive therapy. Triple negative breast cancer (TNBC, ER-, PR- and Her-2-) accounts for approximately 15% of breast cancers and has the poorest outcomes. An hypoxic microenvironment is an important intrinsic component of solid tumours that can result in rapid proliferation of cancer cells and is associated with the lack of oxgyen and abnormal tumour blood vessels. Hypoxia stimulates the hypoxia inducible factor-1α (HIF-1α) that transactivates genes associated with angiogenesis, tumour growth, metastasis, metabolic reprogramming, and treatment resistance. HIF-1α is recognised to induce the expression of carbonic anhydrase IX (CAIX), an enzyme that has been attributed a central role in pH regulation and cancer progression and is particularly pronounced in peri necrotic tumour areas, high-grade BCs. The adaption to hypoxia is governed by multiple transcriptional and post-transcriptional changes in gene expression. Up to 1.5 % of the human genome is estimated to be transcriptionally responsive to hypoxia. Genes and pathways which have been identified as being responsive to hypoxia may have the potential to be used as prognostic or predictive markers, and furthermore, can help identify novel therapeutic targets. The aim of the present study was to gain a better understanding of the transcriptomic and protein pathways associated with CAIX in ER- BC to identify potential therapeutic targets against this aggressive phenotype.
2023-07-31 | E-MTAB-11955 | biostudies-arrayexpress
Project description:We performed single cell RNA sequencing (RNA-seq) for 549 primary breast cancer cells and lymph node metastases from 11 patients with distinct molecular subtypes (BC01-BC02, estrogen receptor positive (ER+); BC03, double positive (ER+ and HER2+); BC03LN, lymph node metastasis of BC03; BC04-BC06, human epidermal growth factor receptor 2 positive (HER2+); BC07-BC11, triple-negative breast cancer (TNBC); BC07LN, lymph node metastasis of BC07) and matched bulk tumors. We separated these single cells into epithelial tumor and tumor-infiltrating immune cells using inferred CNVs from RNA-seq. The refined single cell profiles for the tumor and immune cells provide key expression signatures of breast cancer and the surrounding microenvironment.
2016-12-09 | GSE75688 | GEO