Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA293880 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Imipramine Blue a novel inhibitor that we recently synthesiszed suppressed breast cancer growth and progression by silencing FOXM1 and its associated signaling.
2016-08-10 | GSE72363 | GEO
Project description:Imipramine Blue a novel inhibitor that we recently synthesiszed suppressed breast cancer growth and progression by silencing FOXM1 and its associated signaling. Breast cancer cell-line MDA-MB-231 treated with vehicle (DMSO) and IB, with 2 biological replciates each.
2016-08-10 | E-GEOD-72363 | biostudies-arrayexpress
Project description:Breast cancer is the most common cancer in women and the leading cause of cancer-related deaths in women worldwide. Although survival of breast cancer patients has improved in the last decade, major hurdles remain. Two problems associated with current therapies include acquired resistance and the debilitating side effects of treatment, especially chemotherapy. Therefore, safer treatment options that effectively suppress cancer progression and reduce treatment-associated side effects are much needed. Repurposing of clinically approved or investigational drugs could be one type of effective and safe options for treating cancer patients. Imipramine is a tricyclic antidepressant commonly used for many decades. It is a selective serotonin reuptake inhibitor (SSRI) and inhibits other neurotransmitters. Here, we report that imipramine blocks ER+ and TNBC growth and progression by inhibiting key proteins involved in ER-a signaling, cell cycle progression, and DNA repair and replication. Furthermore, imipramine improved the efficacy of PARP inhibitor therapy in TNBC. This study is the first to show that imipramine is a promising therapeutic option for breast cancer and to define imipramine’s mechanism of action and targets in breast cancer. This pre-clinical study is the basis for a currently ongoing clinical trial testing the efficacy of imipramine for treating breast cancer.
2023-07-06 | GSE190814 | GEO
Project description:Tumors require ample protein synthesis to grow, and aminoacyl-tRNA synthetases, as critical translation factors, are expected to support cancer progression. Unexpectedly, overexpression of seryl-tRNA synthetase (SerRS) suppresses primary tumor growth of breast cancer. However, the effects of SerRS on metastasis have not been studied. We observe a decrease in SerRS expression in breast cancer patient metastases compared to matched primary tumors, suggesting an inhibitory role of SerRS in metastasis. Through mouse metastasis models using breast cancer cell lines overexpressing SerRS, we show that SerRS impedes both primary tumor growth and establishment of metastases. By inducing SerRS overexpression after primary tumor implantation, we demonstrate the potential of SerRS as an anticancer therapeutic. Through tumor RNA-Seq, we identify Wnt signaling among the top SerRS-regulated pathways. Using cell-based studies, we confirm SerRS suppresses Wnt signaling and metastatic processes in breast cancer cells. To our knowledge, this is the first study to show a translation factor can act as both a tumor and metastasis suppressor.
2025-02-19 | GSE264557 | GEO
Project description:Reciprocal interactions between breast cancer cells and the tumor microenvironment are important for cancer progression and metastasis. We report here that the deletion or inhibition of sphingosine kinase 2 (SphK2), which produces sphingosine-1-phosphate (S1P), markedly suppresses syngeneic breast tumor growth and lung metastasis in mice by creating a hostile microenvironment for tumor growth and invasion. SphK2 deficiency decreased S1P and concomitantly increased ceramides, including C16-ceramide, in stromal fibroblasts. Ceramide accumulation suppressed activation of cancer-associated fibroblasts (CAFs) by upregulating stromal p53, which restrained production of tumor-promoting factors to reprogram the tumor microenvironment and restrict breast cancer establishment. Ablation of p53 in SphK2-deficient fibroblasts reversed these effects, enabled CAF activation and promoted tumor growth and invasion. These data uncovered a novel role of SphK2 in regulating non-cell autonomous functions of p53 in stromal fibroblasts and their transition to tumor-promoting CAFs, paving the way for the development of a strategy to target the tumor microenvironment and enhance therapeutic efficacy.
2020-01-01 | GSE136655 | GEO
Project description:The MYC transcription factor is a key regulator of growth during development and a potent cancer driver when its expression is dysregulated. Strategies to inhibit MYC oncogenic activity would mark a significant advance, but decades of efforts to target MYC directly have not been fruitful. Understanding how MYC drives transformation and tumor growth may provide new therapeutic avenues in a variety of cancers. By intersecting two independent genome-wide screens, we identified loss of the chromatin remodeler Chromodomain-Helicase DNA-binding 1 (CHD1) as a potential synthetic lethal target in MYC-driven breast cancer. Knockdown of CHD1 in a xenograft model of MYC-driven breast cancer suppresses tumor growth in vivo. In tissue culture models, we found that knockdown of CHD1 suppresses cell proliferation and induces cell death, specifically when MYC is overexpressed. Mechanistically, we found that CHD1 is required to maintain an open chromatin landscape and a transcriptional program associated with cancer progression in MYC overexpressing breast cells. Follow-up experiments indicate that this synthetic lethality may arise from nucleolar stress and p53 activation. These findings provide new insights on the chromatin-level regulation of MYC-driven breast cancer and uncover CHD1 as a novel synthetic vulnerability and potential therapeutic target.
2026-02-26 | GSE303748 | GEO
Project description:The MYC transcription factor is a key regulator of growth during development and a potent cancer driver when its expression is dysregulated. Strategies to inhibit MYC oncogenic activity would mark a significant advance, but decades of efforts to target MYC directly have not been fruitful. Understanding how MYC drives transformation and tumor growth may provide new therapeutic avenues in a variety of cancers. By intersecting two independent genome-wide screens, we identified loss of the chromatin remodeler Chromodomain-Helicase DNA-binding 1 (CHD1) as a potential synthetic lethal target in MYC-driven breast cancer. Knockdown of CHD1 in a xenograft model of MYC-driven breast cancer suppresses tumor growth in vivo. In tissue culture models, we found that knockdown of CHD1 suppresses cell proliferation and induces cell death, specifically when MYC is overexpressed. Mechanistically, we found that CHD1 is required to maintain an open chromatin landscape and a transcriptional program associated with cancer progression in MYC overexpressing breast cells. Follow-up experiments indicate that this synthetic lethality may arise from nucleolar stress and p53 activation. These findings provide new insights on the chromatin-level regulation of MYC-driven breast cancer and uncover CHD1 as a novel synthetic vulnerability and potential therapeutic target.
2026-02-26 | GSE303747 | GEO
Project description:Breast cancer is the most frequently diagnosed female cancer accounting for 23 % of the total cases and the second leading cause of cancer mortality in the world, particularly in western countries. Since GEPARDUO trial reported the therapeutic benefit of combined doxorubicin and cyclophosphamide regimen in sequential administration with docetaxel, the combination regimen has become a standard therapeutic strategy in neoadjuvant systemic therapy for patients with operable breast cancers regardless of an intrinsic subtype. Although approximately 70% of entire patients are currently receiving the chemotherapy regimen, pathologic complete response (pCR) rate is still low, ranging from 23% to 32.7% due to the high heterogeneity of breast cancers. Therefore, the need for a marker predictive of response to a particular cytotoxic regimen, especially before neoadjuvant chemotherapy, is becoming all the more necessary to optimize therapeutic efficacy and to avoid unnecessary complications caused by systemic therapy. In the study, here we generated the first high-coverage proteomic data for needle biopsy FFPE sample being characterized with identical clinical conditions including chemotherapeutic regimens and the stage classification.
2021-09-08 | PXD013431 | Pride
Project description:Imipramine, a tricyclic antidepressant, has demonstrated antitumoral properties in various preclinical studies (both in vitro and in vivo), although it is not currently approved for cancer treatment. The aim of this experiment is to investigate the transcriptomic changes associated with imipramine treatment (24, 48 and 72 h) in vitro in luminal and triple-negative breast cancer cell models. RNA-seq (raw data), 5 biological replicates per condition.
2026-04-09 | E-MTAB-15351 | biostudies-arrayexpress