Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA293880 | ENA |
REPOSITORIES: ENA
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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: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: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:Metastasis initiates when cancer cells escape from the primary tumor, which requires changes to intercellular junctions. Claudins are transmembrane proteins that form the tight junction, and their expression is reduced in aggressive breast tumors. However, claudins’ roles during breast cancer metastasis remain unclear. We used gain- and loss-of-function genetics in organoids isolated from murine breast cancer models to establish that Cldn7 suppresses invasion and metastasis. Transcriptomic analysis revealed that Cldn7 knockdown induced smooth muscle actin (SMA)-related genes and a broader mesenchymal phenotype. We validated our results in human cell lines, fresh human tumor tissue, bulk RNA-seq, and public single cell RNA-seq data. We consistently observed an inverse relationship between Cldn7 expression and expression of SMA-related genes. Furthermore, knockdown and overexpression of SMA-related genes demonstrated that they promote breast cancer invasion. Our data reveal that Cldn7 suppresses breast cancer invasion and metastasis through negative regulation of SMA-related and mesenchymal gene expression.
2024-09-13 | GSE273512 | GEO
Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis. primary breast tumors vs. bone trephine biopsies
2012-11-09 | E-GEOD-39494 | biostudies-arrayexpress
Project description:BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease. Three 4T1.2 primary mammary tumours and three 4T1.2-Bmp4 primary mammary tumours were analyzed.
2014-06-01 | E-GEOD-51632 | biostudies-arrayexpress
Project description:IL13Rα2 overexpression promotes metastasis of basal-like breast cancers IL13Rα2 depletion in highly metastatic breast cancer cells suppresses lung metastases formation by upregulating TP63 and decreasing their migratory potential
2015-07-28 | GSE57677 | GEO