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C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.
(WILEY, 2019-09-16)
Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome-wide ...
Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor Cell Line Panels.
(HUMANA PRESS INC, 2018-01-01)
Loss-of-function screening using RNA interference or CRISPR approaches can be used to identify genes that specific tumor cell lines depend upon for survival. By integrating the results from screens in multiple cell lines ...
E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2018-04-01)
The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...
Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential.
(CELL PRESS, 2018-04-10)
Tumor necrosis factor (TNF) is an inflammatory cytokine that can signal cell survival or cell death. The mechanisms that switch between these distinct outcomes remain poorly defined. Here, we show that the E3 ubiquitin ...
Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.
(CELL PRESS, 2018-01-30)
Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically ...
Inactivating NF1 Mutations Are Enriched in Advanced Breast Cancer and Contribute to Endocrine Therapy Resistance.
(AMER ASSOC CANCER RESEARCH, 2020-02-01)
PURPOSE: Advanced breast cancer (ABC) has not been subjected to the same degree of molecular scrutiny as early primary cancer. Breast cancer evolves with time and under the selective pressure of treatment, with the potential ...
High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-10-01)
BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly ...
ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942.
(NATURE PUBLISHING GROUP, 2020-01-01)
The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become ...
Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation.
(NATURE PUBLISHING GROUP, 2019-06-20)
The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability ...
Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.
(NATURE PORTFOLIO, 2017-11-30)
Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, ...