A5011226345- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Metabolism, Diabetes, and Cancer
- Radiopharmaceutical Chemistry and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- RNA modifications and cancer
- Cellular Mechanics and Interactions
- Ultrasound and Hyperthermia Applications
- Mesenchymal stem cell research
- Redox biology and oxidative stress
- Glycosylation and Glycoproteins Research
- 3D Printing in Biomedical Research
- Cancer, Lipids, and Metabolism
- Chemokine receptors and signaling
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
University of Michigan–Ann Arbor
2019-2024
Migration and invasion of cancer cells constitute fundamental processes in tumor progression metastasis. Migratory commonly upregulate expression plasminogen activator inhibitor 1 (PAI1), PAI1 correlates with poor prognosis breast cancer. However, mechanisms by which promotes migration remain incompletely defined. Here we show that increased drives rearrangement the actin cytoskeleton, mitochondrial fragmentation, glycolytic metabolism triple-negative (TNBC) cells. In two-dimensional...
Mitochondria produce reactive oxygen species (ROS), which function in signal transduction. Mitochondrial dynamics, encompassing morphological shifts between fission and fusion, can directly impact ROS levels cancer cells. In this study, we identified an ROS-dependent mechanism for how enhanced mitochondrial inhibits triple negative breast (TNBC) cell migration. We found that enforcing TNBC resulted increase intracellular reduced migration the formation of actin-rich migratory structures....
Abstract Cancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer resist standard therapy. We employed a coculture model of estrogen receptor–positive (ER+) breast and mesenchymal stem (MSC) interactions with stromal microenvironments. Using single-cell endogenous engineered biosensors for cellular metabolism, MSCs increased oxidative phosphorylation,...
Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed recapitulate genes proteins, some borrowed others tumor-intrinsic, induced in by direct contact. Protein-protein...
Cancer cells continually sense and respond to mechanical cues from the extracellular matrix (ECM). Interaction with ECM can alter intracellular signaling cascades, leading changes in processes that promote cancer cell growth, migration, survival. The present study used a recently developed composite hydrogel composed of fibrin phase-shift emulsion, termed an acoustically responsive scaffold (ARS), investigate effects local properties on breast signaling. Treatment ARSs focused ultrasound...
Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed recapitulate genes proteins, some borrowed others tumor-intrinsic, induced in by direct contact. Protein-protein...
<div>Abstract<p>Cancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer resist standard therapy. We employed a coculture model of estrogen receptor–positive (ER<sup>+</sup>) breast and mesenchymal stem (MSC) interactions with stromal microenvironments. Using single-cell endogenous engineered biosensors for cellular metabolism, MSCs...
<p>Figure S7. Inhibition of monocarboxylate transporters regulates intracellular and extracellular lactate. Western blot shows expression MCT4 in monocultures MCF7, T47D, HS5, HS27a cells. Images are from adjacent lanes on one gel non-adjacent a second gel. We show β-actin as loading control. B,C) Graphs mean values ± standard deviation for relative concentrations (B) (C) lactate MCF7 cells or co-cultures HS5 treated with 10 µM syrosingopine, an inhibitor MCT1/4, vehicle 3 days. ***...
<p>Figure S6. Flow cytometry data for CSC stains. Cell type of interest is bolded in co-culture comparisons. A) Representative gating scheme ALDH activity, CD24, and CD44 analyses. B-D) MCF7 (B), T47D (C), HCC1428 (HCC, D) cells monoculture versus with MSCs stained CD44. N > 10,000 cells.</p>
<p>Figure S5. Representative images of glucose and ATP FRET reporters in MSCs. Pseudocolor scale depicts high (red) low (blue) CFP lifetime. Scale bar = 50 µm. intracellular (A) (B) HS5 MSCs when co-culture with ER+ breast cancer cells. Cancer cells are unlabeled pseudocolor images.</p>
<p>Figure S7. Inhibition of monocarboxylate transporters regulates intracellular and extracellular lactate. Western blot shows expression MCT4 in monocultures MCF7, T47D, HS5, HS27a cells. Images are from adjacent lanes on one gel non-adjacent a second gel. We show β-actin as loading control. B,C) Graphs mean values ± standard deviation for relative concentrations (B) (C) lactate MCF7 cells or co-cultures HS5 treated with 10 µM syrosingopine, an inhibitor MCT1/4, vehicle 3 days. ***...
<p>Figure S6. Flow cytometry data for CSC stains. Cell type of interest is bolded in co-culture comparisons. A) Representative gating scheme ALDH activity, CD24, and CD44 analyses. B-D) MCF7 (B), T47D (C), HCC1428 (HCC, D) cells monoculture versus with MSCs stained CD44. N > 10,000 cells.</p>
<p>Figure S5. Representative images of glucose and ATP FRET reporters in MSCs. Pseudocolor scale depicts high (red) low (blue) CFP lifetime. Scale bar = 50 µm. intracellular (A) (B) HS5 MSCs when co-culture with ER+ breast cancer cells. Cancer cells are unlabeled pseudocolor images.</p>
<p>Figure S8. Single-cell metabolic responses over time. Cell type of interest is bolded in co-culture comparisons. Cumulative AUC changes NADH lifetime 30 minutes post-treatment 10-minute intervals. For a single cell, each change normalized to the initial lifetime. Table shows median values picoseconds or CFP (ATP) after addition compound. Labels at top table denote relevant comparison column.</p>
<p>Figure S8. Single-cell metabolic responses over time. Cell type of interest is bolded in co-culture comparisons. Cumulative AUC changes NADH lifetime 30 minutes post-treatment 10-minute intervals. For a single cell, each change normalized to the initial lifetime. Table shows median values picoseconds or CFP (ATP) after addition compound. Labels at top table denote relevant comparison column.</p>
<p>Figure S3. ROS quantification for MSCs in monoculture and co-culture. Flow cytometry data detected by CellROX Green HS5 HS27a or co-culture with MCF7 (A), T47D (B), HCC1428 (C) ER+ breast cancer cells. Solid dashed lines depict co-culture, respectively. Cell type of interest is bolded comparisons. N>10,000 cells.</p>
<p>Figure S2. NADH lifetime and ROS quantification for ER+ breast cancer cells with CM MSCs in monoculture co-culture. Cell type of interest is bolded co-culture comparisons. A-B) Histograms HS5 (A) HS27a (B) or MCF7, T47D, HCC1428 (HCC) cells. C-E) MCF7 (C), T47D (D), (HCC, E) control from MSCs. Dashed lines represent solid N>100 cells.</p>
<p>Figure S4. Validation of FRET reporters for intracellular glucose and ATP. Pseudocolor scale depicts high (red) low (blue) CFP lifetime. Scale bar = 50 µm. Symbols show pair-wise comparisons with ****p<0.0001 using one-way ANOVA. A) Representative images box whiskers plots in MCF7 monocultures 0-, 5-, or 25-mM glucose. B) ATP before after addition oligomycin.</p>
<p>Figure S1. Representative images of NADH lifetimes for various experimental conditions. Cell type interest is bolded in co-culture comparisons. Top row denotes cancer cells marked with nuclear mCherry. Pseudocolor scale depicts high (red) and low (blue) lifetime. Scale bar = 50 µm. A) HS5 HS27a MSCs monoculture. B-C) MCF7 (B) or T47D (C) monoculture conditioned media (CM) from listed MSCs. D) HCC1428 (HCC) monoculture, CM MSCs, direct MSCs.</p>
<p>Figure S3. ROS quantification for MSCs in monoculture and co-culture. Flow cytometry data detected by CellROX Green HS5 HS27a or co-culture with MCF7 (A), T47D (B), HCC1428 (C) ER+ breast cancer cells. Solid dashed lines depict co-culture, respectively. Cell type of interest is bolded comparisons. N>10,000 cells.</p>
<p>Figure S1. Representative images of NADH lifetimes for various experimental conditions. Cell type interest is bolded in co-culture comparisons. Top row denotes cancer cells marked with nuclear mCherry. Pseudocolor scale depicts high (red) and low (blue) lifetime. Scale bar = 50 µm. A) HS5 HS27a MSCs monoculture. B-C) MCF7 (B) or T47D (C) monoculture conditioned media (CM) from listed MSCs. D) HCC1428 (HCC) monoculture, CM MSCs, direct MSCs.</p>