A5053144955- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Cell Adhesion Molecules Research
- Extracellular vesicles in disease
- Skin and Cellular Biology Research
- Radiopharmaceutical Chemistry and Applications
- Microfluidic and Bio-sensing Technologies
- Angiogenesis and VEGF in Cancer
- Microtubule and mitosis dynamics
- Force Microscopy Techniques and Applications
- Primary Care and Health Outcomes
- MicroRNA in disease regulation
- Computational Drug Discovery Methods
- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- RNA Research and Splicing
- Metabolomics and Mass Spectrometry Studies
- Tendon Structure and Treatment
- Erythrocyte Function and Pathophysiology
- Interprofessional Education and Collaboration
- Glutathione Transferases and Polymorphisms
Université Laval
2011-2025
Vanderbilt University
2017-2023
Cancer Research Center
2022
Centre hospitalier de l'Université Laval
2022
Hôtel-Dieu de Québec
2008-2022
Cornell University
2013-2018
Centre hospitalier universitaire de Québec
2010-2012
Tumor microvasculature tends to be malformed, more permeable, and tortuous than vessels in healthy tissue, effects that have been largely attributed up-regulated VEGF expression. However, tumor tissue stiffen during solid progression, stiffness is known alter cell behaviors including proliferation, migration, cell-cell adhesion, which are all requisite for angiogenesis. Using vitro, vivo, ex ovo models, we investigated the of matrix on vessel growth integrity Our data indicate angiogenic...
Abstract Communication between the inner cell mass (ICM) and trophoblast layer of blastocyst is known to occur, but its functional consequences on early developmental events unclear. Here we demonstrate that embryonic stem (ES) cells derived from ICM generate shed microvesicles (MVs), a major class extracellular vesicles (EVs), which influence behaviour during implantation process. The MV cargo proteins laminin fibronectin interact with integrins along surfaces trophoblasts, triggering...
Significance Metastasis accounts for most cancer-associated death. To metastasize, cells can move collectively where travel together as cohorts to invade surrounding tissues. However, the mechanisms by which are unclear. Utilizing a combination of in vitro, ex vivo, and silico approaches, we demonstrated that cancer cell collective invasion is regulated energetic states leader–follower cells. Leader require more energy than follower cells, forward leader consumes depletes its available...
Cell migration in a three-dimensional matrix requires that cells either remodel the surrounding fibers and/or squeeze between to move. Matrix degradation, remodeling, and changes cell shape each require expend energy. While significant research has been performed understand cellular molecular mechanisms guiding metastatic migration, less is known about energy regulation utilization during cancer migration. Here we introduce use of genetically encoded fluorescent biomarkers, PercevalHR pHRed,...
Cell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices migrating cells. Here, we investigate cellular energetics decision-making in confined spaces. Theoretical and experimental data show energetic costs for through spaces are mediated by balance between cell matrix compliance as well degree of spatial confinement direct decision-making. Energetic costs, driven work needed generate force...
One of the key steps during tumour metastasis is cell migration and invasion, which require actin cytoskeletal reorganization. Among critical protrusion structures are filopodia, act like sensory organs to communicate with extracellular microenvironment participate in fundamental functions such as adhesion, spreading three-dimensional environment. Fascin main actin-bundling protein filopodia. Using high-throughput screening, here we identify characterize small molecules that inhibit activity...
During intravasation, cancer cells cross the endothelial barrier and enter circulation. Extracellular matrix stiffening has been correlated with tumor metastatic potential; however, little is known about effects of stiffness on intravasation. Here, we utilize in vitro systems, a mouse model, specimens from patients breast cancer, RNA expression profiles The Cancer Genome Atlas Program (TCGA) to investigate molecular mechanism by which promotes cell Our data show that heightened increases...
Significance Alternative splicing is the main mechanism that drives protein diversity; however, little known about physiological cues control splicing. Here, we show stiffness of extracellular matrix mediates in cells both vitro and vivo. mediated by occurs through phosphorylation regulatory factors, serine/arginine rich (SR) proteins, depends on PI3K signaling pathway. Because SR family proteins are conserved among vertebrates invertebrates to also be involved genome stabilization,...
Tumor metastasis is the major cause of mortality cancer patients, being responsible for ∼90% all deaths. One key steps during tumor cell migration which requires actin cytoskeletal reorganization. Among critical protrusion structures are antenna‐like filopodia. Fascin protein main actin‐bundling in Here we report development fascin‐specific small‐molecules that inhibit interaction between fascin and actin. These inhibitors block vitro actin‐binding activities fascin, mouse models....
During metastasis, cells can use proteolytic activity to form tube-like “microtracks” within the extracellular matrix (ECM). Using these microtracks, migrate unimpeded through stroma. To investigate molecular mechanisms of microtrack migration, we developed an in vitro three-dimensional (3D) micromolded collagen platform. When tend unidirectionally. Because focal adhesions are primary mechanism by which interact with ECM, examined roles several adhesion molecules driving unidirectional...
Vascular endothelial growth factor (VEGF) can mediate cell migration, proliferation, and angiogenesis. During cancer progression, VEGF production is often increased to stimulate the of new blood vessels supply growing tumors with additional oxygen nutrients they require. Extracellular matrix stiffening also occurs during tumor however, crosstalk between mechanics signaling remains poorly understood. Here, we show that stiffness heightens downstream response by altering receptor-2 (VEGFR-2)...
ABSTRACT Tumor vasculature is known to be more permeable than the found in healthy tissue, which turn can lead a aggressive tumor phenotype and impair drug delivery into tumors. While stiffening of stroma surrounding solid tumors has been reported increase vascular permeability, mechanism this process remains unclear. Here, we utilize an vitro model stiffening, ex ovo culture, mouse investigate molecular by matrix alters endothelial barrier function. Our data indicate that increased...
Abstract Although intratumoral genomic heterogeneity can impede cancer research and treatment, less is known about the effects of phenotypic heterogeneities. To investigate role cell migration heterogeneities in metastasis, we phenotypically sorted metastatic breast cells into two subpopulations based on ability. typically considered to be associated with when injected orthotopically vivo, weakly migratory subpopulation metastasized significantly more than highly subpopulation. mechanism...
Abstract Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation metabolites that reprogram tumor microenvironment (TME) and drive cancer could facilitate development precision nutrition approaches. Using Hi-MYC prostate mouse model, we demonstrated an obesogenic high-fat diet (HFD) rich in saturated fats accelerates c-MYC–driven invasive through...
Keratins are intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatocyte and hepatoma cell IFs made solely keratins 8/18 (K8/K18), the hallmark all simple epithelia. Cell attachment/spreading (adhesion) migration involve formation focal adhesions at sites integrin interactions with extracellular matrix, actin adaptors such talin vinculin, signaling molecules adhesion kinase (FAK) member(s) protein C (PKC) family. Here, we...
Cell mechanical activity generated from the interplay between extracellular matrix (ECM) and actin cytoskeleton is essential for regulation of cell adhesion, spreading migration during normal cancer development. Keratins are intermediate filament (IF) proteins epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatic IFs made solely keratins 8/18 (K8/K18), hallmarks all simple epithelia. Notably, our recent work on these cells has revealed key regulatory function...
Extracellular vesicles released by cancer cells have recently been implicated in the differentiation of stromal to their activated, cancer-supporting states. Microvesicles, a subset extracellular from plasma membrane cells, contain biologically active cargo, including DNA, mRNA, and miRNA, which are transferred recipient induce phenotypic change behavior. While it is known that microvesicles can alter cell phenotype, little about how physical properties tumor microenvironment affect...
The Ras homolog (Rho) small GTPases coordinate diverse cellular functions including cell morphology, adhesion and motility, cycle progression, survival, apoptosis via their role in regulating the actin cytoskeleton. upstream regulators for many of these are unknown. ARHGEF17 (also known as TEM4) is a Rho family guanine nucleotide exchange factor (GEF) implicated migration, cell–cell junction formation, mitotic checkpoint. In this study, we characterize regulation by TEM4. We demonstrate that...
Arterial stiffening accompanies both aging and atherosclerosis, age-related of the arterial intima increases RhoA activity cell contractility contributing to increased endothelium permeability. Notably, statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors whose pleiotropic effects include disrupting small GTPase activity; therefore, we hypothesized statin simvastatin could be used attenuate inhibit deleterious matrix stiffness on endothelial barrier function....
Cells receive mechanical cues from their extracellular matrix (ECM), which direct migration, differentiation, apoptosis, and in some cases, the transition to a cancerous phenotype. As result, there has been significant research develop methods tune properties of ECM understand cell-ECM dynamics more deeply. Here, we show that ionizing radiation can reduce stiffness an ex vivo tumor vitro collagen matrix. When non-irradiated cancer cells were seeded irradiated matrix, adhesion, spreading,...
During cancer progression, metastatic cells leave the primary tumor and invade into fibrous extracellular matrix (ECM) within surrounding stroma. This ECM network is highly heterogeneous, interest in understanding how this can affect cell behavior has increased past several decades. However, replicating heterogeneity proven challenging. Here, we designed utilized a method to create well-defined interface between two distinct regions of high- low-density collagen gels mimic heterogeneities...
Traction force microscopy (TFM) is a method used to study the forces exerted by cells as they sense and interact with their environment. Cell play role in processes that take place over wide range of spatiotemporal scales, so it desirable TFM makes use imaging modalities can effectively capture dynamics associated these processes. To date, confocal has been modality choice perform 3D settings, although multiple factors limit its coverage. We propose traction optical coherence (TF-OCM) novel...