Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360963 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Estrogen Receptor α (ERα)-mTOR signaling crosstalk rewires cancer cell metabolism providing a mechanism underlying obesity-associated postmenopausal breast cancer
| PRJNA362645 | ENA
Project description:Estrogen Receptor α (ERα)-mTOR signaling crosstalk rewires cancer cell metabolism providing a mechanism underlying obesity-associated postmenopausal breast cancer [ChIP-seq]
| PRJNA362644 | ENA
Project description:Obesity is a risk factor for postmenopausal ERα (+) breast cancer. The metabolites from serum that contribute to this risk and how these factors affect ERα signaling are not known. Using whole metabolite profiling and a detection panel for proteins, we identified biomarkers that were differentially present in serum from obese vs. non-obese postmenopausal women, and we validated these factors in two separate cohorts of postmenopausal women who either developed breast cancer or those who were obese and lost weight after the onset of menopause. In vitro assays identified free fatty acids (FFAs), in particular oleic acid (OA) as serum factors that correlate with increased proliferation and aggressiveness in ERα(+) breast cancer cells by. FFAs activated both ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which target ERα and mTOR signaling, was able to block changes induced by FFAs. In fact, PaPEs were more effective in the presence of FFAs, suggesting a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ERα-(+) breast cancer in postmenopausal women. Our findings provide a basis for preventing or inhibiting obesity-associated breast cancer by using PaPEs that would reverse these newly appreciated metabolic vulnerabilities of breast tumors in obese postmenopausal women.
2020-01-11 | GSE93510 | GEO
Project description:Obesity is a risk factor for postmenopausal ERα (+) breast cancer. The metabolites from serum that contribute to this risk and how these factors affect ERα signaling are not known. Using whole metabolite profiling and a detection panel for proteins, we identified biomarkers that were differentially present in serum from obese vs. non-obese postmenopausal women, and we validated these factors in two separate cohorts of postmenopausal women who either developed breast cancer or those who were obese and lost weight after the onset of menopause. In vitro assays identified free fatty acids (FFAs), in particular oleic acid (OA) as serum factors that correlate with increased proliferation and aggressiveness in ERα(+) breast cancer cells by. FFAs activated both ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which target ERα and mTOR signaling, was able to block changes induced by FFAs. In fact, PaPEs were more effective in the presence of FFAs, suggesting a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ERα-(+) breast cancer in postmenopausal women. Our findings provide a basis for preventing or inhibiting obesity-associated breast cancer by using PaPEs that would reverse these newly appreciated metabolic vulnerabilities of breast tumors in obese postmenopausal women.
2020-01-11 | GSE93505 | GEO
Project description:Obesity is a risk factor for postmenopausal ERα (+) breast cancer. Molecular mechanisms activated by the factors from serum that contribute to this risk and how these mechanisms affect ERα signaling are yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in serum samples, which enabled us to focus on factors that were differentially present in serum from cancer-free vs. breast cancer susceptible and obese vs. non-obese post-menopausal women. These studies combined with in vitro assays identified free fatty acids (FFAs), as serum factors that correlate with increased proliferation and aggressiveness in ERα(+) breast cancer cells by. FFAs activated both ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which target ERα and mTOR signaling, was able to block changes induced by FFAs. In fact, PaPEs were more effective in the presence of FFAs, suggesting a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ERα-(+) breast cancer in postmenopausal women. Our findings provide a basis for preventing or inhibiting obesity-associated breast cancer by using PaPEs that would reverse these newly appreciated metabolic properties of breast tumors in obese postmenopausal women.
2019-05-11 | GSE114372 | GEO
Project description:Combined menopausal hormone therapy is associated with increased breast cancer risk in postmenopausal women. In our previous studies, progesterone receptor membrane component 1 (PGRMC1) was shown to play a role in progestins’ mode of action, resulting in enhanced proliferation of breast cancer cells. Here we describe a potential mechanism by which PGRMC1 contributes to breast cancer progression via interaction with prohibitins, inhibiting their function as transcription factor repressors, thereby facilitating estrogen receptor alpha (ERα) transcriptional activity and enhancing oncogenic signaling upon treatment with certain progestins, such as norethisterone and dydrogesterone.
2022-02-16 | PXD028537 | Pride
Project description:Estrogen receptor and mTOR signaling rewires cancer metabolism in obesity-associated breast cancer
| PRJNA471101 | ENA
Project description:Endocrine therapies targeting the proliferative effect of 17β-estradiol (17βE2) through estrogen receptor α (ERα) are the most effective systemic treatment of ERα-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through a molecular mechanism that is not yet fully understood. The long-term estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors (AIs) in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERα. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were influenced by transcription factors known to be involved in acquired resistance or cell proliferation (e.g. IRF1 and E2F1, respectively) but, notably, not by canonical ERα transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)- to pS167-ERα were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERα-negative status, early response to letrozole and recurrence after tamoxifen treatment. This study proposes a mechanism for acquired resistance to estrogen deprivation that is coordinated across biological levels and independent of canonical ERα function. LTED (long term estrogen deprived) cell line was generated from MCF-7 cells by long-term culture under estrogen deprivated conditions. And RNA samples were obtained after 3, 15, 30, 90, 120, 150 and 180 days.
2010-09-01 | E-GEOD-20361 | biostudies-arrayexpress
Project description:The Estrogen Receptor alpha (ERα) controls key cellular functions in hormone responsive breast cancer by assembling in large functional multiprotein complexes. ERα ligands are classified as agonists and antagonist, according to the response they elicit, thus the molecular characterization of the of ERα nuclear iteractome composition following estrogen and antiestrogen stimulation whose is needed to understand their effects on estrogen target tissues, in particular breast cancer. To this aim interaction proteomics coupled to mass spectrometry (MS) was applied to map the ERα nuclear interacting partners in MCF7 breast cancer cell nuclei following estrogen and antiestrogen stimuli.
2020-09-02 | PXD018709 | Pride
Project description:The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription. This set contains 12 microarray samples. 3 controls, 3 estrogen stimulated, 3 Bortezomib stimulated, 3 Bortezomib + estrogen stimulated
2011-11-22 | E-GEOD-30931 | biostudies-arrayexpress