Publications by authors named "Sharrell B Lee"
Unlabelled: Epithelial-to-mesenchymal transition (EMT) contributes significantly to chemotherapy resistance and remains a critical challenge in treating advanced breast cancer. The complexity of EMT, involving redundant pro-EMT signaling pathways and its paradox reversal process, mesenchymal-to-epithelial transition (MET), has hindered the development of effective treatments. In this study, we utilized a Tri-PyMT EMT lineage-tracing model and single-cell RNA sequencing (scRNA-seq) to comprehensively analyze the EMT status of tumor cells.
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- Radiation therapy (RT) combined with immune checkpoint inhibitors (ICIs) shows promise for treating non-small cell lung cancer (NSCLC), but the specific mechanisms behind this combination therapy are not well understood.
- Researchers found an optimal dose of RT that led to tumor shrinkage and improved survival in NSCLC models when paired with ICIs, highlighting the importance of lung-resident club cells in this process.
- They discovered that specific proteins secreted by club cells not only inhibit immunosuppressive myeloid cells but also boost anti-tumor immune responses, suggesting that these findings could inform future clinical trials of ICIs in NSCLC patients.
Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial.
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- Epigenetic changes play a significant role in breast cancer progression, particularly in the aggressive subtype known as triple-negative breast cancer (TNBC), where EZH2 is identified as a key epigenetic modulator.
- Inhibiting EZH2 can reduce the ability of cancer cells to spread and also helps them adopt a less aggressive, more treatable state by promoting the expression of GATA3, making them more responsive to hormone therapies.
- The research highlights that certain subtypes of TNBC, especially EZH2 basal-like 1 and mesenchymal subtypes, are particularly sensitive to EZH2 inhibition, suggesting the potential for EZH2-targeted therapies in treating metastatic TNBC.
Metastases are responsible for the majority of breast cancer-associated deaths. The contribution of epithelial-to-mesenchymal transition (EMT) in the establishment of metastases is still controversial. To obtain evidence of EMT in metastasis, we established an EMT lineage tracing (Tri-PyMT) model, in which tumor cells undergoing EMT would irreversibly switch their fluorescent marker from RFP to GFP due to mesenchymal-specific Cre expression.
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- The use of immune checkpoint inhibitors, specifically targeting the PD-1/PD-L1 axis, is being explored in early-stage non-small-cell lung cancer (NSCLC) due to their success in advanced stages.
- Research conducted on early-stage NSCLC patients and a Kras mutant mouse model revealed a shift in the immune environment over time, with early increases in PD-1+ T cells but later showing more immunosuppressive traits as the tumor progressed.
- PD-1 inhibition not only slowed tumor growth and improved survival rates but also altered the behavior of immune cells, showcasing the necessity for timing in targeting this immune pathway during lung cancer's early stages.
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- About 15-20% of non-small cell lung cancer (NSCLC) patients benefit from current targeted therapies, highlighting the need for new drug targets.
- Researchers used RNA-deep sequencing to find gene expression changes in lung tissue, discovering that Matrix Metalloproteinase 14 (MMP14) was significantly overexpressed in tumor tissues.
- Inhibiting MMP14 reduced lung cancer cell invasion and tumor incidence in mouse models, suggesting that targeting the MMP14-HB-EGF signaling pathway could be a promising therapeutic approach for NSCLC.
Purpose: Bone marrow-derived progenitor cells, including VEGFR2 endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models.
View Article and Find Full Text PDFEmerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer.
View Article and Find Full Text PDFTumor endothelial cells (ECs) promote cancer progression in ways beyond their role as conduits supporting metabolism. However, it is unknown how vascular niche-derived paracrine factors, defined as angiocrine factors, provoke tumor aggressiveness. Here, we show that FGF4 produced by B cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notch ligand Jagged1 (Jag1) on neighboring ECs.
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- Metastatic tumors create supportive environments for their spread using bone marrow cells, but even tumors that don't spread can form similar environments that actually block metastasis.
- In this study, the Gr1(+) myeloid cells from bone marrow are shown to produce thrombospondin-1 (Tsp-1), a factor that helps prevent metastasis when induced by tumor-secreted prosaposin.
- A 5-amino acid peptide derived from prosaposin was identified that boosts Tsp-1 production in Gr1(+) cells, showing promise as a potential treatment to suppress metastatic cancer.