Biology subjects

Foster, B.

Publications and source records attributed to Foster, B..

At least 19 recordsLinked to original sources

bioRxiv2025

Matrix Metalloproteinase (MMP) inhibition rescues endothelial glycocalyx damage and reduces neutrophil infiltration in sepsis-associated acute kidney injury

Endothelial glycocalyx (eGlx), a carbohydrate-rich endothelial coat, maintains vascular homeostasis, and its disruption contributes to several vascular diseases. We previously identified matrix metalloproteinase (MMP) 2 and 9-mediated eGlx shedding as a key mechanism in human glomerular endothelial cell (GEnC) damage and kidney dysfunction in diabetes. Here, we sought to determine whether this mechanism contributes to renal and systemic microvascular endothelial cell injury in sepsis-AKI. Sepsis-AKI was induced in mice by lipopolysaccharide (LPS) injection. Confocal microscopy demonstrated glomerular and peritubular eGlx damage, and increased circulating SDC4 demonstrated systemic eGlx shedding. These were associated with enhanced mRNA expression of eGlx components (syndecans 1 and 4) and endothelial inflammatory markers, Intercellular and Vascular Cell Adhesion Molecules (ICAM and VCAM) in the kidney. Additionally, sepsis-AKI markers, serum creatinine and urea, were increased. We found that renal and circulating MMP9, but not MMP2, levels were raised in sepsis-AKI. Moreover, MMP9 staining colocalises with neutrophil, endothelial and mesangial staining in glomeruli in sepsis-AKI. Treatment with MMP2 and 9 inhibitor 1, 1h before LPS injection, prevented glomerular, peritubular and systemic eGlx damage in sepsis-AKI. MMP inhibition also attenuated glomerular leucocyte numbers in sepsis-AKI. We confirmed increased MMP9 activity, shedding of eGlx syndecan 1 and elevated angiopoietin 2 levels, an endothelial damage marker, in sepsis-AKI in humans. Moreover, we used human glomerular endothelial cells (GEnC) in vitro to demonstrate that human sepsis-AKI serum directly damages GEnC eGlx. Our studies confirm that MMP-mediated eGlx damage is a key contributor to renal and systemic microvascular dysfunction in sepsis-AKI and represents a potential therapeutic target for protecting the microvasculature.

cell biology↗

bioRxiv2025

Notch expression during ctenophore development gives insight into its ancestral function

The canonical Notch pathway is a juxtacrine signaling module with widely conserved roles maintaining progenitor cell populations, promoting binary cell fate decisions, and establishing tissue boundaries. This pathway emerged in Metazoan lineages, although many molecular components and regulators existed prior to that divergence. Given that the vast majority of Notch studies focus on bilaterians, it is unclear when or how Notch gained its developmental signaling functions. To clarify the ancestral function of Notch, we turned to an early branching Metazoan -- the ctenophore Mnemiopsis leidyi -- and conducted structural analyses of putative Notch components to evaluate predicted signaling potential. We characterized gene expression of these components with in situ hybridization and show they are expressed during late embryogenesis. Using hybridization chain reaction (HCRTM), we examine MlNotch expression relative to canonical transcriptional targets and putative stem cell markers and identify differential expression patterns at a cellular resolution. Pharmacological inhibition reveals zones of active and inactive MlNotch during late embryonic development. Our results suggest that Notch evolved its signaling potential by the Metazoan divergence and is likely involved in regulating progenitor cell populations and coordinating developmental fate decisions.

developmental biology↗

bioRxiv2024

Simulating CD8 T Cell Exhaustion: A Comprehensive Approach

Immunotherapy has revolutionised the treatment of multiple cancer types, however, these treatments only work for a proportion of patients and biomarkers to predict response are lacking. One correlate of response is the reinvigoration of a subset of CD8 T cells that have an exhausted phenotype and impaired functionality. In order to develop new therapies, reproducible models are required to identify candidate target genes that enables the reversal of key hallmarks of T cell exhaustion. Here we describe the development of an in vitro model by chronically stimulating T cells with their cognate antigen and performed an in depth temporal phenotypic characterisation. This model recapitulates many of the critical hallmarks of exhaustion, including increased expression of canonical exhaustion surface markers, impaired proliferation, reduced cytokine production, decreased release of cytotoxic granules, and metabolic alterations, including dysfunctional mitochondria. These exhaustion hallmarks were validated using an in vivo model and a gene signature identified which robustly define the shared in vitro and in vivo exhausted state. Critically, this signature is also observed in tumour infiltrating T cells from multiple human tumour types, validating the translational potential of this model for discovering and triaging new therapies.

immunology↗

bioRxiv2024

European Farmhouse Brewing Yeasts Form a Distinct Genetic Group

The brewing industry is constantly evolving, driven by the quest for novel flavors and fermentation characteristics that cater to evolving consumer preferences. This study explores the genetic and phenotypic diversity of European farmhouse yeasts, traditionally used in rural brewing practices and maintained outside of pure culture industrial yeast selection. We isolated landrace brewing yeast strains from diverse geographical locations across Europe, including Norway, Lithuania, Latvia, Russia, and also included African farmhouse brewing strains from Ghana. Our genomic analysis using long-read and short-read whole genome sequencing uncovered a genetically distinct group that diverges from industrial brewing yeasts. This group, which is closely related to ale brewing strains, is preliminarily named the "European Farmhouse" group and shows greater predicted admixture from Asian fermentation strains. Through genomic and phenotypic analyses, including flavor metabolite analysis via HS-GC-MS, sugar metabolite analysis via HPLC, and wort fermentation analysis, we found a broad spectrum of fermentation capabilities, from rapid and efficient fermentation to unique aroma and flavor compound profiles, potentially offering novel traits for brewing applications. This study highlights the importance of preservation of brewing cultural heritage knowledge and resources including yeast cultures. Key PointsO_LIA large set of geographically diverse farmhouse brewing strains were characterized C_LIO_LINorwegian and Baltic farmhouse brewing strains form a distinct genetic group C_LIO_LIFarmhouse strains show considerable diversity in fermentation and flavour formation C_LI

microbiology↗

bioRxiv2023

A novel in vivo system to study coral biomineralization in the starlet sea anemone (Nematostella vectensis)

Coral reefs are important for maintaining healthy marine ecosystems and are declining rapidly due to increasing environmental stresses. Coral conservation efforts require a mechanistic understanding of how these stresses may disrupt biomineralization, but progress in this area has been slow primarily because corals are not easily amenable to laboratory research. Some cellular characteristics of biomineralization are well characterized, such as the role of carbonic anhydrases, the polarized secretion of ions, and the secretion of "intrinsically disordered proteins" (IDPs) into extracellular microenvironments. We highlight how the starlet sea anemone (Nematostella vectensis) can serve as a tractable model to interrogate the cellular mechanisms of coral biomineralization. We have developed transgenic constructs using genes involved in biomineralization from several animal phyla that can be injected into Nematostella zygotes. These constructs are designed so translated proteins may be purified using TEV protease or Histidine tags to study their physicochemical properties. Using a fluorescent tag, we confirm ectopic expression of the coral biomineralizing protein SpCARP1 in live Nematostella embryos and adults and demonstrate via calcein staining that calcium ions co-localize with SpCARP1 in carbonate and calcium enriched seawater. Our findings suggest that SpCARP1 can induce the formation of amorphous calcium carbonate precursors in N. vectensis, consistent with its suspected role in the early stages of coral biomineralization. These results lay a fundamental groundwork for establishing N. vectensis as a novel in vivo system to explore the evolutionary and cellular mechanisms of biomineralization, improve coral conservation efforts, and even develop novel biomaterials. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/560932v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1170b4eorg.highwire.dtl.DTLVardef@1e7491corg.highwire.dtl.DTLVardef@1710cd1org.highwire.dtl.DTLVardef@100743b_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2023

The RPA complex orchestrates K63-linked deubiquitination via ZUP1

Ubiquitin signaling is regulated by deubiquitinating enzymes (DUBs), which can edit or remove ubiquitin from substrates. Recently, ZUP1 was discovered as the founding and only member of a novel DUB class that cleaves long K63-linked ubiquitin chains, with a putative role in DNA repair. However, ZUP1 has poor activity on its own, suggesting additional mechanisms exist to promote its activity in cells. Here, using a range of cellular, biochemical, and structural proteomics approaches, we show that ZUP1 directly interacts with the RPA complex, a single-stranded DNA binding protein complex involved in DNA replication and multiple DNA repair processes. Functionally, the ZUP1-RPA complex interaction dramatically stimulates ZUP1 K63-linked DUB activity, which occurs through S1 and S1 site communication. Collectively, our results suggest a mechanism that couples sensing of ssDNA to the activation of K63-linked deubiquitination via the ZUP1-RPA complex.

biochemistry↗

bioRxiv2022

Genomic features predict bacterial life history strategies in soil, as identified by metagenomic stable isotope probing

Bacteria catalyze the formation and destruction of soil organic matter, but the bacterial dynamics in soil that govern carbon (C) cycling are not well understood. Life history strategies explain the complex dynamics of bacterial populations and activities based on tradeoffs in energy allocation to growth, resource acquisition, and survival. Such tradeoffs influence the fate of soil C, but their genomic basis remains poorly characterized. We used multi-substrate metagenomic DNA stable isotope probing to link genomic features of bacteria to their C acquisition and growth dynamics. We identify several genomic features associated with patterns of bacterial C acquisition and growth, notably genomic investment in resource acquisition and regulatory flexibility. Moreover, we identify genomic tradeoffs defined by numbers of transcription factors, membrane transporters, and secreted products, which match predictions from life history theory. We further show that genomic investment in resource acquisition and regulatory flexibility can predict bacterial ecological strategies in soil.

microbiology↗

bioRxiv2021

TEMPO: A system to sequentially label and genetically manipulate vertebrate cell lineages

During development, regulatory factors appear in a precise order to determine cell fates over time. To investigate complex tissue development, one should not just label cell lineages but further visualize and manipulate cells with temporal control. Current strategies for tracing vertebrate cell lineages lack genetic access to sequentially produced cells. Here we present TEMPO (Temporal Encoding and Manipulation in a Predefined Order), an imaging-readable genetic tool allowing differential labelling and manipulation of consecutive cell generations in vertebrates. TEMPO is based on CRISPR and powered by a cascade of gRNAs that drive orderly activation/inactivation of reporters/effectors. Using TEMPO to visualize zebrafish and mouse neurogenesis, we recapitulated birth-order-dependent neuronal fates. Temporally manipulating cell-cycle regulators in mouse cortex progenitors altered the proportion and distribution of neurons and glia, revealing the effects of temporal gene perturbation on serial cell fates. Thus, TEMPO enables sequential manipulation of molecular factors, crucial to study cell-type specification. One-Sentence SummaryGaining sequential genetic access to vertebrate cell lineages.

developmental biology↗

bioRxiv2021

CircHIPK3 dysregulation of the miR-30c/DLL4 axis is essential for KSHV lytic replication

Non-coding RNA (ncRNA) regulatory networks are emerging as critical regulators of gene expression. These intricate networks of ncRNA:ncRNA interactions modulate multiple cellular pathways and impact the development and progression of multiple diseases. Herpesviruses, including Kaposis sarcoma-associated herpesvirus, are adept at utilising ncRNAs, encoding their own as well as dysregulating host ncRNAs to modulate virus gene expression and the host response to infection. Research has mainly focused on unidirectional ncRNA-mediated regulation of target protein-coding transcripts; however, we have identified a novel host ncRNA regulatory network essential for KSHV lytic replication in B cells. KSHV-mediated upregulation of the host cell circRNA, circHIPK3, is a key component of this network, functioning as a competing endogenous RNA of miR-30c, leading to increased levels of the miR-30c target, DLL4. Dysregulation of this network highlights a novel mechanism of cell cycle control during KSHV lytic replication in B cells. Importantly, disruption at any point within this novel ncRNA regulatory network has a detrimental effect on KSHV lytic replication, highlighting the essential nature of this network and potential for therapeutic intervention.

microbiology↗

bioRxiv2021

Kveik brewing yeasts demonstrate wide flexibility in beer fermentation temperature and flavour metabolite production and exhibit enhanced trehalose accumulation

AO_SCPLOWBSTRACTC_SCPLOWTraditional Norwegian Farmhouse ale yeasts, also known as kveik, have captured the attention of the brewing community in recent years. Kveik were recently reported as fast fermenting thermo- and ethanol tolerant yeasts with the capacity to produce a variety of interesting flavour metabolites. They are a genetically distinct group of domesticated beer yeasts of admixed origin with one parent from the "Beer 1" clade and the other unknown. While kveik are known to ferment wort efficiently at warmer temperatures, its range of fermentation temperatures and corresponding flavour metabolites produced, remain uncharacterized. In addition, the characteristics responsible for its increased thermotolerance remain largely unknown. Here we demonstrate variation in kveik strains at a wide range of fermentation temperatures and show not all kveik strains are equal in fermentation performance, flavour metabolite production and stress tolerance. Furthermore, we uncovered an increased capacity of kveik strains to accumulate intracellular trehalose, which likely contributes to its increased thermo- and ethanol tolerances. Taken together our results present a clearer picture of the future opportunities presented by Norwegian kveik yeasts and offer further insight into their applications in brewing.

microbiology↗

bioRxiv2020

The DOE JGI Metagenome Workflow

The DOE JGI Metagenome Workflow performs metagenome data processing, including assembly, structural, functional, and taxonomic annotation, and binning of metagenomic datasets that are subsequently included into the Integrated Microbial Genomes and Microbiomes (IMG/M) comparative analysis system (I. Chen, K. Chu, K. Palaniappan, M. Pillay, A. Ratner, J. Huang, M. Huntemann, N. Varghese, J. White, R. Seshadri, et al, Nucleic Acids Rsearch, 2019) and provided for download via the Joint Genome Institute (JGI) Data Portal (https://genome.jgi.doe.gov/portal/). This workflow scales to run on thousands of metagenome samples per year, which can vary by the complexity of microbial communities and sequencing depth. Here we describe the different tools, databases, and parameters used at different steps of the workflow, to help with interpretation of metagenome data available in IMG and to enable researchers to apply this workflow to their own data. We use 20 publicly available sediment metagenomes to illustrate the computing requirements for the different steps and highlight the typical results of data processing. The workflow modules for read filtering and metagenome assembly are available as a Workflow Description Language (WDL) file (https://code.jgi.doe.gov/BFoster/jgi_meta_wdl.git). The workflow modules for annotation and binning are provided as a service to the user community at https://img.jgi.doe.gov/submit and require filling out the project and associated metadata descriptions in Genomes OnLine Database (GOLD) (S. Mukherjee, D. Stamatis, J. Bertsch, G. Ovchinnikova, H. Katta, A. Mojica, I Chen, and N. Kyrpides, and T. Reddy, Nucleic Acids Research, 2018). IMPORTANCEThe DOE JGI Metagenome Workflow is designed for processing metagenomic datasets starting from Illumina fastq files. It performs data pre-processing, error correction, assembly, structural and functional annotation, and binning. The results of processing are provided in several standard formats, such as fasta and gff and can be used for subsequent integration into the Integrated Microbial Genome (IMG) system where they can be compared to a comprehensive set of publicly available metagenomes. As of 7/30/2020 7,155 JGI metagenomes have been processed by the JGI Metagenome Workflow.

bioinformatics↗

bioRxiv2020

Isolation of potential plant growth-promoting bacteria from nodules of legumes grown in arid Botswana soil

As the world population increases, improvements in crop growth and yield will be needed to meet rising food demands, especially in countries that have not developed agricultural practices optimized for their own soils and crops. In many African countries, farmers improve agricultural productivity by applying synthetic fertilizers and pesticides to crops, but their continued use over the years has had serious environmental consequences including air and water pollution as well as loss of soil fertility. To reduce the overuse of synthetic amendments, we are developing inocula for crops that are based on indigenous soil microbes, especially those that enhance plant growth and improve agricultural productivity in a sustainable manner. We first isolated environmental DNA from soil samples collected from an agricultural region to study the composition of the soil microbiomes and then used Vigna unguiculata (cowpea), an important legume crop in Botswana and other legumes as "trap" plants using the collected soil to induce nitrogen-fixing nodule formation. We have identified drought-tolerant bacteria from Botswana soils that stimulate plant growth; many are species of Bacillus and Paenibacillus. In contrast, the cowpea nodule microbiomes from plants grown in these soils house mainly rhizobia particularly Bradyrhizobium, but also Methylobacterium spp. Hence, the nodule microbiome is much more limited in non-rhizobial diversity compared to the soil microbiome, but also contains a number of potential pathogenic bacteria.

microbiology↗

bioRxiv2020

The trajectory of cortical GABA levels across thelifespan: An individual participant datameta-analysis of edited MRS studies

GABA is the principal inhibitory neurotransmitter in the human brain and can be measured with Magnetic Resonance Spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age-range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, 8 suitable datasets were integrated to generate a model of the trajectory of GABA across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show the lifespan trajectory of GABA involves an early period of rapid increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models. The information gained will provide a general framework to inform expectations of future studies based on the age of the population being studied.

neuroscience↗

bioRxiv2020

Right lateralized posterior parietal theta-gamma coupling during sustained attention in mice

Sustained attention is supported by circuits in the frontoparietal attention network. In human and primate studies, the right posterior parietal cortex (PPC) shows dominance for sustained attention, and phase-amplitude coupling (PAC) throughout the frontoparietal network correlates with performance on attention tasks. Here we evaluate oscillatory dynamics of bilateral PPC in mice during the 5-Choice Serial Reaction Time Task (5-CSRTT). Right PPC theta-gamma PAC (TG-PAC) and gamma power were independently elevated to a greater degree than the left PPC during the period prior to a correct response and were significantly correlated with accuracy in both simple and difficult tasks. Greater task difficulty was also associated with greater hemispheric asymmetry in TG-PAC, favoring the right PPC. These findings highlight the engagement of PPC with sustained attention in mice, reflected by increases in TG-PAC and gamma power, with maximal expression in the right hemisphere.

neuroscience↗

bioRxiv2019

Impact of soil salinity on the cowpea nodule-microbiome and the isolation of halotolerant PGPR strains to promote plant growth under salinity stress

Four soil samples (SS-1--SS-4) isolated from semi-arid soils in Punjab, Pakistan were used as inocula for cowpea (Vigna unguiculata L.) grown under salinity stress to analyze the composition of bacteria in the rhizosphere and within nodules through cultivation-dependent and cultivation-independent methods. Two cowpea varieties, 603 and the salt-tolerant CB 46, were each inoculated with four different native soil samples, and data showed that plants inoculated with soil samples SS-2 and SS-4 grew better than plants inoculated with soil samples SS-1 and SS-3. Bacteria were isolated from both soils and nodules, and 34 of the 51 original isolates tested positive for PGPR traits in plate assays with many exhibiting multiple plant growth-promoting properties. A number of isolates were positive for all PGPR traits tested. For the microbiome studies, environmental DNA (eDNA) was isolated from SS-1 and SS-4, which represented the extremes of the Pakistan soils to which the plants responded, and by 16S rRNA gene sequencing analysis were found to consist mainly of Actinobacteria, Firmicutes, and Proteobacteria. However, sequencing analysis of eDNA isolated from cowpea nodules established by the trap plants grown in the four Pakistan soils indicated that the nodule microbiome consisted almost exclusively of Proteobacterial sequences, particularly Bradyrhizobium. Yet, many other bacteria including Rhizobium, Mesorhizobium, Pseudomonas, as well as Paenibacillus, Bacillus as well as non-proteobacterial genera were isolated from the nodules of soil-inoculated cowpea plants. This discrepancy between the bacteria isolated from cowpea nodules (Proteobacteria and non-Proteobacteria) versus those detected in the nodule microbiome (Proteobacteria) needs further study.

plant biology↗

bioRxiv2019

Distinct Narrow and Broadband Gamma Responses in Human Visual Cortex

High frequency activity (> 30 Hz) in the neocortical local field potential, typically referred to as the gamma range, is thought to have a critical role in visual perception and cognition more broadly. Historically, animal studies recording from visual cortex documented clear narrowband gamma oscillations (NBG; [~]20-60 Hz) in response to visual stimuli. However, invasive measurements from human neocortex have highlighted a different broadband or high gamma response (BBG; [~]70-150+ Hz). Growing evidence suggests these two forms of gamma response are distinct, but often conceptually or analytically conflated as the same gamma response. Furthermore, recent debate has highlighted that both the occurrence and spectral properties of gamma band activity in visual cortex appears to be dependent on the attributes and class of presented visual stimuli. Using high-density intracranial recordings from human visual cortex, we integrate and extend these findings, dissociating the spectral, temporal and functional properties of NBG and BBG activity. We report results from two experiments, manipulating visual stimulus attributes (contrast-varying gratings) and class (object categories) dissecting the differential properties of NBG and BBG responses. NBG oscillations were only reliably recorded for grating stimuli, while their peak frequency varied with contrast level. Whereas BBG activity was observed in response to all stimulus classes tested, with no systematic change in its spectral features. Temporally, induced NBG was sustained throughout stimulus presentation, in opposition to a more transient response for the BBG. These findings challenge the ubiquity of gamma activity in visual cortex, by clearly dissociating oscillatory and broadband effects.\n\nSignificance StatementNeocortical narrowband gamma oscillations ([~]20-60 Hz) have been implicated in vision and cognition as a mechanism for synchronizing brain regions. Efforts to study this phenomenon have revealed an additional high-gamma range response ([~]70-150+ Hz), which is broadband and non-oscillatory. These different gamma range activities are often conflated in support of the same functional role. Using invasive recordings from human visual cortex, we show that narrow and broadband gamma can be dissociated by spectral, temporal and functional response properties. While broadband gamma responses were more transient to the presentation of all stimuli, narrowband gamma responses were sustained and only occurred reliably to grating stimuli. These differences have important implications for the study, analysis and interpretation of neocortical gamma range activity.

neuroscience↗

bioRxiv2018

Dynamic Electrical Stimulation of Sites in Visual Cortex Produces Form Vision in Sighted and Blind Humans

Visual cortical prosthetics (VCPs) offer the promise of restoring sight to blind patients. Electrical stimulation of a single site in visual cortex can reliably produce a percept of a spot of light in a fixed visual field location, known as a phosphene. Researchers developing VCPs have assumed that multiple phosphenes produced by concurrent stimulation of multiple sites in visual cortex can combine to form a coherent form, like pixels in a visual display. However, existing data do not support this assumption. Therefore, we developed a novel stimulation paradigm for VCPs termed dynamic current steering in which the visual form to be conveyed is traced on the surface of visual cortex by electrically stimulating electrodes in a dynamic sequence. When tested in sighted and blind subjects, this method of stimulating visual cortex allowed for the immediate recognition of a variety of letter shapes without training and with high accuracy.\n\nOne Sentence SummaryStimulating human visual cortex using dynamic patterns of activity allows both blind and sighted patients to perceive visual percepts of useful forms.

neuroscience↗

bioRxiv2018

CTC Marker CD117/c-kit Represents a Prostate Cancer Stem-Like Subpopulation Driving Progression, Migration, and TKI Resistance

Cancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/c-kit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used LNCaP-C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population. Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.

cancer biology↗