A5020406142- MicroRNA in disease regulation
- Circular RNAs in diseases
- Cancer, Lipids, and Metabolism
- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- Kruppel-like factors research
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Estrogen and related hormone effects
- Click Chemistry and Applications
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Advanced Breast Cancer Therapies
- Extracellular vesicles in disease
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Cyclopropane Reaction Mechanisms
- Cancer Immunotherapy and Biomarkers
- Brain Metastases and Treatment
University of Notre Dame
2017-2023
University of Colorado Denver
2009-2023
Cancer Research Institute
2018-2020
University of Chicago
2013-2014
University of Colorado Anschutz Medical Campus
2009-2014
University of Colorado Cancer Center
2012
The University of Texas MD Anderson Cancer Center
2012
University of Colorado Boulder
2011
University of Colorado Health
2008
University of Rochester
2008
The androgen receptor (AR) is widely expressed in breast cancers and has been proposed as a therapeutic target estrogen alpha (ER) negative that retain AR. However, controversy exists regarding the role of AR, particularly ER + tumors. Enzalutamide, an AR inhibitor impairs nuclear localization was used to elucidate preclinical models positive cancer.We examined protein ratios primary relation response endocrine therapy. effects inhibition with enzalutamide were vitro cancer express AR.In...
Abstract The transcription factor ZEB1 is normally not expressed in epithelial cells. When inappropriately carcinomas, initiates to mesenchymal transition due its ability repress E-cadherin and other genes involved polarity. Recently, ZEB2 have been identified as direct targets of the microRNA-200c family. We find that miR-200c levels are high well-differentiated endometrial, breast, ovarian cancer cell lines, but extremely low poorly differentiated Low or absent results aberrant expression...
miR-200c and other members of the miR-200 family promote epithelial identity by directly targeting ZEB1 ZEB2, which repress E-cadherin genes involved in polarity. Loss is often observed carcinoma cells that have undergone to mesenchymal transition (EMT). Restoration such leads a reduction stem cell-like characteristics, reduced migration invasion, increased sensitivity taxanes. Here we investigate functional role novel targets aggressive behavior breast endometrial cancer cells.Putative...
We focus on unique roles of miR-200c in breast, ovarian, and endometrial cancers. Members the miR-200 family target ZEB1, a transcription factor which represses E-cadherin other genes involved polarity. demonstrate that double negative feedback loop between ZEB1 is functional some, but not all cell lines. Restoration to aggressive cancer cells causes decrease migration invasion. These effects are independent status. Additionally, we observe restoration ovarian adhesion laminin. have...
A therapeutic intervention that could decrease tumor burden and increase sensitivity to chemotherapy would have a significant impact on the high morbidity rate associated with ovarian cancer. miRNAs emerged as potential candidates due their ability downregulate multiple targets involved in progression chemoresistance. miRNA-200c (miR-200c) is downregulated cancer cell lines stage III tumors, low miR-200c correlates poor prognosis. increases taxanes vitro by targeting class β-tubulin gene...
Chemotherapy prior to immune checkpoint blockade (ICB) treatment appears improve ICB efficacy but resistance remains a clinical challenge and is attributed highly plastic myeloid cells associating with the tumor microenvironment (TIME). Here we show by CITE-seq single-cell transcriptomic trajectory analyses that neoadjuvant low-dose metronomic chemotherapy (MCT) leads characteristic co-evolution of divergent cell subsets in female triple-negative breast cancer (TNBC). Specifically, identify...
Anoikis is apoptosis initiated upon cell detachment from the native extracellular matrix. Since survival basement membrane required for metastasis, ability to resist anoikis contributes metastatic potential of breast tumors. miR-200c, a potent repressor epithelial mesenchymal transition, expressed in luminal cancers, but lost more aggressive basal-like, or triple negative cancers (TNBC). We previously demonstrated that miR-200c restores sensitivity TNBC cells by directly targeting...
Abstract Breast cancer brain metastases (BCBM) have a 5-20 year latency and account for 30% of mortality; however, mechanisms governing adaptation to the microenvironment remain poorly defined. We combine time-course RNA-sequencing BCBM development with Drosophila melanogaster genetic screen, identify Rab11b as functional mediator metastatic adaptation. Proteomic analysis reveals that controls cell surface proteome, recycling proteins required successful interaction microenvironment,...
Abstract The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution crucial for brain metastasis. Here, we report powerful in this setting caused by epigenetic upregulation glutamate decarboxylase 1 (GAD1), regulator the GABA neurotransmitter pathway. In cell-based culture and metastasis models, found downregulation DNA methyltransferase DNMT1 induced microenvironment–derived...
Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression well documented, effect aging extracellular matrix (ECM) has been overlooked. This study shows that breast ECM alone sufficient to drive normal human mammary epithelial (KTB21) more invasive and cancer-like phenotype, while promoting motility invasiveness MDA-MB-231 cells. Decellularized from aged mice leads loss E-cadherin membrane localization KTB21 cells, increased...
The tumor microenvironment (TME), the dynamic tissue space in which exists, plays a significant role initiation, and is key contributor cancer progression; however, little known about tumor-induced changes adjacent stroma. Herein, TME were explored at morphologic molecular level to further understand progression. Tumor-adjacent mammary glands (TAG) displayed altered branching morphology, expansion of myofibroblasts, increased mammosphere formation, broadly suggesting field effect. FACS...
With evolutionary drug resistance impacting efforts to treat disease, the need for small molecules that exhibit novel molecular mechanisms of action is paramount. In this study, we combined scaffold-directed synthesis with a hybrid experimental and transcriptome analysis identify bis-spirooxindole cyclopropanes inhibit cancer cell proliferation through disruption ribosomal function. These findings demonstrate value an integrated, biologically inspired assay strategy accelerated...
Abstract Lacking targetable molecular drivers, triple-negative breast cancer (TNBC) is the most clinically challenging subtype of cancer. In this study, we reveal that Death Effector Domain-containing DNA-binding protein ( DEDD ), which overexpressed in > 60% TNBCs, drives a mitogen-independent G1/S cell cycle transition through cytoplasm localization. The gain cytosolic enhances cyclin D1 expression by interacting with heat shock 71 kDa 8 (HSC70). Concurrently, interacts Rb family...
Abstract Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression well documented, effect aging extracellular matrix (ECM) has been overlooked. Here, we show first time that breast ECM sufficient to drive normal mammary epithelial (KTB21) more invasive and cancer-like phenotype, while promoting motility invasiveness MDA-MB-231 cells. E-cadherin membrane localization was lost KTB21 cultured decellularized from aged mice....
Abstract Background: MicroRNA-200c directly targets ZEB1, an epithelial to mesenchymal (EMT)-inducing transcriptional repressor of E-cadherin and other key determinates identity polarity. Therefore, restoration miR-200c results in repression dramatic reduction migration invasion, increased sensitivity microtubule targeting chemotherapeutics. We hypothesized that addition additional genes contribute its myriad effects on maintaining the phenotype by repressing genes. Results: performed...
564 Background: The androgen receptor (AR) is detected by immunohistochemistry in approximately 75% of all invasive breast cancer; with ~88% ER+ tumors expressing AR. Potent inhibition AR activity could be a therapeutic strategy ER+/AR+ cancer. MDV3100 an signaling inhibitor (ARSI), which inhibits via three mechanisms: binding to AR, nuclear translocation, and AR-DNA binding. has demonstrated overall survival benefit men post-docetaxel prostate Methods: Two cancer cell lines, MCF7 BCK4...
GRAPHICAL ABSTRACT SUMMARY Breast cancer brain metastases (BCBM) have a 5-20 year latency and account for up to 30% of mortality. Developing new therapeutics requires molecular understanding adaptation the microenvironment. Here, we combined RNA-sequencing BCBM development with reverse genetic screen in Drosophila melanogaster identified Rab11b, an endosomal recycling protein, as mediator metastatic adaptation. We show that disseminated cells up-regulate Rab11b early after arrival brain,...