A5010761495- Estrogen and related hormone effects
- Endometrial and Cervical Cancer Treatments
- 14-3-3 protein interactions
- RNA Research and Splicing
- Neuroendocrine Tumor Research Advances
- Genomics and Chromatin Dynamics
- Lung Cancer Research Studies
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- Computational Drug Discovery Methods
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- Molecular Biology Techniques and Applications
- Plant Molecular Biology Research
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Sarcoma Diagnosis and Treatment
Huntsman Cancer Institute
2017-2025
University of Utah
2017-2025
Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank patient-derived xenografts (PDXs) and matched organoid cultures from represent greatest unmet need: endocrine-resistant, treatment-refractory metastatic breast cancers. leverage PDXs PDX-derived organoids (PDxO) for drug screening is feasible cost-effective with in vivo validation. Moreover, we demonstrate feasibility using these models precision oncology...
Small-cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among subtypes largely unexplored. In this study, we aimed to determine whether vulnerabilities between can be therapeutically exploited.We performed steady state metabolomics on tumors isolated from distinct genetically engineered mouse models (GEMM) representing the MYC- and MYCL-driven of SCLC. Using genetic...
Background Breast cancer (BC) continues to be a major health concern with 250,000 new cases diagnosed annually in the USA, 75% of which are hormone receptor positive (HR+), expressing estrogen alpha (ER) and/or progesterone (PR). Although ER-targeted therapies available, 30% patients will develop resistance, underscoring need for non-ER/estrogen-based treatments. Notably, HR+BCs exhibit poor lymphocyte infiltration and contain an immunosuppressive microenvironment, contributes limited...
Steroid hormone receptors are simultaneously active in many tissues and capable of altering each other's function. Estrogen receptor α (ER) glucocorticoid (GR) expressed the uterus, their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression GR is associated poor prognosis. Dexamethasone reduced normal growth vivo; however, this inhibition was abolished estrogen-induced hyperplasia. We observed low...
Abstract Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression, however, the molecular mechanisms underlying ER's regulatory are poorly understood. In breast cells, ER genomic binding is enabled by FOXA1 GATA3, but transcription factors that control cells remain unknown. We previously identified ETV4 as candidate factor controlling here we explore functional importance of ETV4. Homozygous deletion ETV4, using CRISPR/Cas9, led to...
Abstract The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes ASPSCR1::TFE3. We demonstrate that VCP a likely...
Estrogen receptor 1 (
Transcriptional enhancers can regulate individual or multiple genes through long-range three-dimensional (3D) genome interactions, and these interactions are commonly altered in cancer. Yet, the functional relationship between changes 3D associated with regulatory regions differential gene expression appears context-dependent. In this study, we used HiChIP to capture active of endometrial cancer cells response estrogen treatment uncovered significant strongly enriched for receptor alpha (ER,...
Objective Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival of less than 5%. Transcriptomic analysis has identified two clinically relevant molecular subtypes PDAC: classical and basal-like. The subtype characterised by more favourable prognosis better response to chemotherapy the basal-like subtype. also expresses higher levels lineage specifiers that regulate endodermal differentiation, including nuclear receptor hepatocyte factor 4 α (HNF4α)....
Abstract Model systems that recapitulate the complexity of human tumors and reality variable treatment responses are urgently needed to better understand cancer biology develop more effective therapies. Here we report development characterization a large bank patient-derived xenografts (PDX) matched organoid cultures from represent some greatest unmet needs in breast research treatment. These include endocrine-resistant, treatment-refractory, metastatic cancers and, cases, multiple tumor...
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype with peak recurrence as metastatic disease within the first few years of diagnosis. Androgen receptor (AR) expression increased in anchorage-independent cells TNBC preclinical models. Both AR knockdown and inhibition lead to reduced invasion vitro, tumorigenicity, less vivo Transforming growth factor β (TGFβ) pathway gene signatures also during survival both vitro models circulating tumor (CTCs) from patients emergence...
The chronic phase of myeloid leukemia (CP-CML) is characterized by the excessive production maturating cells. As CML stem/progenitor cells (LSPCs) are poised to cycle and differentiate, LSPCs must balance conservation differentiation avoid exhaustion, similar normal hematopoiesis under stress. Since BCR-ABL1 tyrosine kinase inhibitors (TKIs) eliminate differentiating but spare BCR-ABL1-independent LSPCs, understanding mechanisms that regulate LSPC may inform strategies LSPCs. Upon performing...
The c-Myc protooncogene places a demand on glucose uptake to drive glucose-dependent biosynthetic pathways. To meet this demand, protein (Myc henceforth) drives the expression of transporters, glycolytic enzymes, and represses thioredoxin interacting (TXNIP), which is potent negative regulator uptake. A Mychigh/TXNIPlow gene signature clinically significant as it correlates with poor clinical prognosis in triple-negative breast cancer (TNBC) but not other subtypes cancer, suggesting...
Activating estrogen receptor alpha (ER; also known as ESR1) mutations are present in primary endometrial and metastatic breast cancers, promoting estrogen-independent activation of the receptor. Functional characterizations cancer have established unique molecular phenotypic consequences receptor, yet impact ER has not been fully explored. In this study, we used CRISPR-Cas9 to model clinically prevalent ER-Y537S mutation compared results with ER-D538G discover allele-specific differences...
The majority of clinical cancer specimens are preserved as formalin-fixed paraffin-embedded (FFPE) samples. For molecular tests to have wide-reaching impact, they must be applicable FFPE material. Accurate quantitative measurements RNA derived from is challenging because low yields and high amounts degradation. Here, we present FFPEcap-seq, a method specifically designed for sequencing capped 5′ ends FFPEcap-seq combines enzymatic enrichment RNAs with template switching create libraries. We...
Summary Steroid hormone receptors are simultaneously active in many tissues and capable of altering each other’s function. Estrogen receptor α (ER) glucocorticoid (GR) expressed the uterus their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression GR is associated poor prognosis. Dexamethasone reduced normal growth vivo ; however, this inhibition was abolished estrogen-induced hyperplasia. We observed low...
Abstract Most endometrial cancers express the hormone receptor estrogen alpha (ER) and are driven by excess signaling. However, evaluation of response in cancer cells has been limited availability hormonally responsive vitro models, with one cell line, Ishikawa, being used most studies. Here, we describe a novel, adherent endometrioid (EEC) line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression functionally responds to induction over range passages. also demonstrate this...
<p>ER mutants do not affect proliferation, but down-regulate proteins associated with movement and impact migration</p>
<p>Supplementary Materials and Methods</p>
<p>Differentially expressed genes from in vitro RNA-seq experiments</p>
<p>Identification of novel therapeutic targets in ER active and mutant endometrial cancer</p>
<p>Comparison of mutant ER regulated genes and by sustained estrogen signaling</p>
<p>Mutant ESR1 generation: gBlock used for template amplification</p>