Biology subjects

Dai, D.

Publications and source records attributed to Dai, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Mitochondrial transfer mediates metabolic communication between beta cells and islet macrophages

Pancreatic islet macrophages support islet homeostasis and adapt their metabolic program in response to environmental cues, including beta cell released factors. Intercellular mitochondrial transfer is a biological process that modulates cellular responses. To test whether beta cells, which are strongly secretory, transfer mitochondria to islet macrophages, we generated mice with beta cell-specific expression of mitochondrial GFP (PhAMfloxIns1Cre). We demonstrate that beta cells transfer mitochondria to islet macrophages in vivo and in vitro. Diabetogenic stressors did not alter the frequency of mitochondrial transfer and macrophages containing beta cell-derived GFP exhibit increased protein synthesis rates. RNA-seq identified upregulation of activity-regulated cytoskeleton associated protein (Arc) in macrophages receiving beta cell-derived mitochondria, while disruption of actin cytoskeleton dynamics prevented mitochondrial transfer. Together, these findings identify mitochondrial transfer as a previously unrecognized mechanism of beta cell-macrophage communication that may contribute to islet homeostasis and immune regulation.

cell biology↗

bioRxiv2026

19F Ultrafast MAS NMR Reveals the Dynamic Basis of pH-Dependent Regulation in Proteorhodopsin

19F NMR spectroscopy is a powerful approach for studying complex biomolecular systems because of its high sensitivity, exceptional responsiveness to local structural changes, and simplified spectra. Here, we demonstrate the application of 19F ultrafast MAS NMR to 5-fluorotryptophan-labelled proteorhodopsin reconstituted in lipid bilayers. By assigning 9 of the 10 tryptophan resonances, pH-dependent analyses of chemical shifts, line shapes, and conformational exchange reveal the dynamics of two functionally important residues: W34 in the interprotomer His-Asp-Trp triad and W98 within the retinal-binding pocket. The results identify W34 as a dynamic regulator of proton transport and support a model in which slow ring flipping on the seconds timescale transiently modulates the W34-H75 interaction, thereby acting as a pH-dependent molecular throttle. The spectral characteristics of W98 further suggest that it functions as a dynamic regulator of the photocycle within the retinal-binding pocket. Beyond these mechanistic insights, we show that a MAS rate of 100 kHz markedly enhances the resolution of this 19F-labelled membrane protein. Combined with a simple chemical-shift scoring metric and advanced, linear-scaling AF-QM/MM-based 19F chemical shift calculations of all sites within this protein, this workflow provides a robust and broadly applicable framework for characterizing membrane protein structure and dynamics in native-like lipid environments. TABLE OF CONTENT GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/739351v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@18cc7bborg.highwire.dtl.DTLVardef@18cf6fforg.highwire.dtl.DTLVardef@1abe960org.highwire.dtl.DTLVardef@166a39c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2026

Unearthing a fungal giant: Dianjunaceae fam. nov., a novel Paleocene lineage of Xylariales harbouring Dianjunus rex gen. et sp. nov.

During mycological surveys in Yunnan Province, China, specimens of a fungus producing massive, upright stromata up to 50 cm high and individually 2.2 Kg in weight were sampled. Through an integrative taxonomic approach combining detailed morphology, multilocus phylogeny (ITS, LSU, RPB2, TUB2), and phylogenomic analyses, this fungus is proposed as the new species Dianjunus rex gen. et sp. nov., the type of the new family Dianjunaceae (Xylariales). Phylogenetic analyses robustly place Dianjunaceae as a distinct sister clade to Graphostromataceae. Divergence time estimation dates the origin of this family to the early Paleocene ([~]65 Mya), coinciding with the post-K-Pg extinction period, when an estimated 75% of all plant and animal species went extinct, and a significant ecological reorganization of life on earth happened. The stromata of D. rex represent the largest fructifications documented within the Ascomycota, significantly expanding the known morphological range of the Xylariales. The study provides a comprehensive description, including a nodulisporium-like anamorph with periconiella-like branching patterns, and discusses the taxons phylogenetic placement, and distinctive morphology. This discovery highlights the unexplored fungal diversity in East Asian forests.

microbiology↗

bioRxiv2026

Plant-parasitic nematodes produce functional mimics of plant PSK peptides to facilitate parasitism

Root-knot nematodes are obligate plant parasites that cause substantial agricultural losses worldwide. They induce highly specialized, metabolically hyperactive feeding sites within host roots, which serve as their sole source of nutrients throughout their life cycle. The formation and maintenance of these feeding sites depend on the manipulation of host developmental pathways by nematode-derived secretions. Phytosulfokines (PSKs) are small plant peptide hormones that regulate cell division, tissue expansion, and growth responses, processes essential for feeding site development. Here, we identify root-knot nematode genes predicted to encode peptides with a conserved PSK functional motif. These genes are predominantly expressed during the early stages of infection and localize to secretory glands, suggesting a role in early parasitism. Moreover, silencing PSK-like gene expression reduces root gall formation and nematode reproduction. Together, these findings reveal that root-knot nematodes deploy PSK-like peptides as virulence factors to promote successful parasitism, providing the first report of PSK peptide mimicry in any plant pathogen.

plant biology↗

bioRxiv2026

Resistance Breaking in Root-knot Nematodes Carries a Fitness Cost Associated with Defective Feeding Site Development

Root-knot nematodes (RKNs) cause an estimated 157 billion dollars in annual yield losses worldwide. In tomato, resistance to RKNs is conferred by the single dominant resistance gene Mi-1, which has been widely integrated into commercial cultivars. Prolonged and widespread use of Mi-1 has led to the emergence of resistance-breaking populations in tomato fields worldwide; however, the consequences of resistance breaking for nematode performance on susceptible hosts remain poorly understood. Here, we compared infection outcomes of two closely related strains of Meloidogyne javanica, VW4 (Mi-1-avirulent; wild-type) and VW5 (Mi-1-virulent; resistance-breaking), on three susceptible hosts: tomato, cucumber, and rice. Across all hosts, VW5 produced significantly fewer eggs than VW4, revealing a fitness cost associated with Mi-1 virulence. Light and transmission electron microscopy of tomato and cucumber galls revealed impaired feeding site establishment by VW5. Consistent with these observations, transcriptomic profiling showed that VW5 infection induced weaker host transcriptional reprogramming and lacked gene expression signatures associated with effective suppression of plant defense responses. Together, these findings demonstrate that adaptation to Mi-1-mediated resistance incurs a fitness cost on susceptible plants and is accompanied by impaired feeding site formation and altered host reprogramming. Furthermore, these results establish VW4 and VW5 as a powerful resource for understanding nematode genes and pathways required for successful parasitism and feeding site development.

plant biology↗

bioRxiv2025

6mA demethylase Mi-NMAD-1 modulates nematode development and parasitism through the transcription factor Mi-nhr-118

N6-methyladenine (6mA) DNA methylation has emerged as an important epigenetic mark in eukaryotes, but its biological role in plant-parasitic nematodes remains largely unexplored. Here, we demonstrate that 6mA methylation is essential for the embryonic development and parasitic ability of Meloidogyne incognita. Silencing of the 6mA demethylase genes minmad-1 significantly reduced egg hatching, revealing that 6mA-mediated regulation is required for nematode development. Transcriptome analyses showed that minmad-1 knockdown downregulated genes involved in embryogenesis, RNA biosynthesis, and cell differentiation, suggesting a critical role of 6mA in developmental gene regulation. Among the transcription factors affected by minmad-1 silencing, Mi-nhr-118, a nuclear hormone receptor orthologous to C. elegans nhr-118, was identified as a key regulator of embryonic development. Functional assays confirmed that RNAi or host-induced gene silencing (HIGS) of Mi-nhr-118 led to developmental arrest, reduced gall and egg mass formation, and impaired infectivity across multiple Meloidogyne species. ChIP-seq analysis revealed that Mi-nhr-118 directly binds to promoters of genes associated with cellular regulation and developmental signaling. Several downstream targets, including transcription factors (Mi_23621.1, Mi_39647.1) and genes implicated in metabolic and signaling processes (Mi_03067.1, Mi_08398.1), were shown to be essential for both embryogenesis and parasitism. Functional enrichment analyses of Mi-nhr-118 target genes indicated suppression of immune-related signaling, carbohydrate recognition, and glycoprotein biosynthetic pathways following gene silencing. Collectively, these findings establish Mi-nhr-118 as a central regulator linking 6mA-mediated epigenetic control to development and parasitism in M. incognita.

molecular biology↗

bioRxiv2025

Genomic and Transcriptomic Insights into the Evolution and Parasitic Strategy of the Woody-Plant Nematode Pratylenchus vulnus

The root-lesion nematode Pratylenchus vulnus parasitizes a wide range of hosts including woody perennials such as walnut (Juglans regia) and grapevine (Vitis vinifera), significantly damaging roots and reducing yields. Here, we present a high-quality, chromosome-level genome assembly of P. vulnus (61.7 Mb across six chromosomes). Comparative genomic analysis revealed high collinearity in protein-coding genes between P. vulnus and the root-knot nematode Meloidogyne graminicola, indicating a closer evolutionary relationship with this sedentary endoparasite. Large chromosomal regions in P. vulnus lack synteny with other nematode genomes, have comparatively low GC content (<30%), and are enriched in genes with unique or lineage-specific functions. Transcriptome analysis highlighted dynamic, stage-specific expressions of genes involved in parasitism, development, and metabolism. Additionally, we identified an extensive repertoire of putative effector genes and characterized lineage-specific expansions of cell wall-degrading enzyme families. Overall, these findings provide insight into the genome organization, chromosome evolution, and parasitism-related gene repertoire in a woody-plant parasitizing nematode.

plant biology↗

bioRxiv2025

N6-Methyladenine DNA modification regulates pathogen virulence in nematodes

Understanding the global regulatory mechanisms that control pathogen virulence gene expression is essential for elucidating the molecular basis of pathogenicity. N6-methyladenine (6mA) plays a crucial role in regulating gene expression in response to various environmental stresses; however, its role in pathogen virulence remains largely unexplored. Here, we report the widespread occurrence of 6mA across 17 nematode isolates and map its genomic landscape in six notorious agriculturally important pathogen root-knot nematodes (RKNs). We demonstrated that 6mA is characterized by a conserved GAG motif across nematodes, but exhibits species-specific distribution patterns and distinct effects on gene expression. In particular, its enrichment in transposable elements differs between polyploid and diploid nematodes, suggesting lineage-specific epigenetic regulation potentially associated with polyploidy. We further identified two functional 6mA demethylases, MiNMAD-1 and MiNMAD-2, and confirmed their catalytic activity and active sites. Host-induced gene silencing of minmad-1 significantly increased plant resistance to three polyploid RKN species. A detailed functional analysis revealed that minmad-1 knockdown disrupted virulence gene expression during the parasitic stage, thereby reducing nematode infectivity. Together, our findings suggest 6mA demethylase as a key epigenetic regulator of RKNs virulence, providing new insights into nematode biology and offering promising targets for the development of sustainable control strategies. Significance Statement6mA methyltransferase regulates the expression of virulence genes in certain pathogenic bacteria and plays a critical role in their infectivity. However, the regulation of virulence gene expression in eukaryotic pathogens, particularly plant pathogens, remains poorly understood. Most studies on pathogen virulence have focused on individual effectors, with little insight into global regulatory mechanisms. Here, we demonstrate that 6mA broadly shapes virulence gene expression patterns in polyploid RKNs. Moreover, transgenic tobacco, tomato, and rice plants expressing dsRNA against nematode demethylases showed significantly enhanced resistance to RKNs. These findings establish 6mA demethylase as a promising epigenetic target for controlling plant-parasitic nematodes.

molecular biology↗

bioRxiv2025

Developmental dynamic transcriptomics reveals multiple effectors and transcription factors critical for Ditylenchus destructor parasitism

Plant-parasitic nematodes (PPNs) pose a major threat to global agricultural production, yet fundamental research on their biology remains limited. The origin and evolutionary trajectory of PPNs remain elusive, largely due to the scarcity of chromosome-level genomic data. Among them, migratory PPNs are considered a key transitional form between free-living and obligate parasitic lifestyles, as they exhibit both plant parasitism and fungal feeding behaviors. In this study, we assembled a chromosome-level genome of the sweet potato rot nematode Ditylenchus destructor and confirmed the presence of four chromosomes through Hi-C scaffolding and karyotype analysis. Comparative genomic analysis with two other migratory PPNs, Bursaphelenchus xylophilus and Aphelenchoides besseyi, revealed that the Nigon elements in B. xylophilus are largely conserved with those of the model organism Caenorhabditis elegans, while D. destructor and A. besseyi exhibit extensive Nigon element rearrangements. These rearrangements were strongly correlated with patterns of protein sequence collinearity. Moreover, transcriptomic profiling across five developmental stages of D. destructor identified numerous stage-specific effectors and transcription factors. Functional analysis via RNA interference demonstrated that many of these genes play essential roles in embryogenesis and parasitic activity. Together, our results provide valuable genomic and transcriptomic resources for studying PPNs, uncovering critical insights into their genome evolution and parasitism-related gene functions, and laying a crucial foundation for advancing the understanding of PPN biology and their impact on agricultural systems.

genomics↗

bioRxiv2025

A Chromosome-scale Reference Genome of Meloidogyne hapla reveals localized recombination hotspots enriched with Effector Proteins

Root-knot nematodes (Meloidogyne spp.) are among the most destructive agricultural pests that cause significant yield losses across a wide range of crops. Meloidogyne hapla, a diploid species, is a valuable model for studying root-knot nematodes due to its parasitic diversity, small genome, and a reproductive strategy that facilitates genetic analysis. Here, we present a high-quality chromosome-scale assembly of M. hapla, generated using multiple sequencing platforms-PacBio HiFi, ONT, Illumina and HiC. The 59 Mb assembly comprises 16 chromosome-length scaffolds, notably lacking canonical telomeric repeats. Instead, we identified a tandem 16-mer repeat mainly present at scaffold ends, suggesting an alternative system for chromosome-end maintenance. Genetic linkage analysis of F2 populations derived from crosses between M. hapla strains validated the assembly but also revealed anomalies indicating chromosome structure differences between parental isolates such as fissions, fusions, and rearrangements. This analysis also revealed sharply delineated zones of high recombination on most chromosome arms. We also identified 1,258 genes encoding putative secreted proteins (PSP), which should be enriched in genes involved in host interaction and pathogenicity. Most of the PSP genes had orthologs in other plant parasitic nematode species, and the majority were pioneers, lacking known functional domains. Notably, we found that PSPs are significantly enriched in high-recombination zones, possibly facilitating their rapid evolution. Overall, our study provides new insights into the genome structure of diploid root-knot nematodes and highlights the interplay between genome architecture, recombination, and parasitism. These findings raise new questions about how genetic and genomic adaptations drive the success of rootknot nematodes as plant parasites.

plant biology↗

bioRxiv2025

Quantitative systems pharmacology modeling of pyrrolobenzodiazepine antibody-drug conjugates targeting BCMA

Antibody-drug conjugates (ADCs) are novel therapeutics combining two molecules linked together: an antibody that provides targeting to specific cells, and a cytotoxic drug (warhead) that can deconjugate from the antibody and kill those cells. The warhead by itself would be too nonspecific and toxic; the antibody by itself would be insufficiently effective at killing the cells. As more and more ADCs enter the drug development pipeline, understanding the mechanistic reasons behind efficacy and toxicity is critical to evaluating both successful and failed trials. Here, we have developed a mechanistic computational model of ADCs, and specifically parameterize it using data for MEDI2228, an anti-BCMA antibody conjugated to pyrrolobenzodiazepine (PBD) warheads. We build the model to track not only the concentrations of ADC and its released warhead drug inside and outside the cell, but also to track the recent history of the warhead, so that we can distinguish between pathways for on-target and bystander (nontargeted) cell killing. We show that this effect is predicted to be small under in vitro conditions due to dilution in large volumes of media, but likely to form a significant part of both targeted and nontargeted cell killing in vivo, where the extracellular volume has less of a dilution effect. We also explore the impact of key design parameters of ADCs, including drug to antibody ratio (DAR), warhead potency, and lipophilicity; this analysis demonstrates the balance needed between killing of targeted and nontargeted cells. Using this quantitative systems pharmacology model, we can generate insights for optimization of ADC design and determine which factors are most critical to efficacy and toxicity, leading to more informed and rational development of cancer therapies.

systems biology↗

bioRxiv2025

High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

In contrast to the rapid advancements in mesoscale connectomic mapping of the mammalian brain, similar mapping the peripheral nervous system has remained challenging due to the bodys size and complexity. Here, we present a high-speed blockface volumetric imaging system with an optimized workflow of whole-body clearing, capable of imaging the entire adult mouse at micrometer resolution within 40 hours. Three-dimensional reconstruction of individual spinal fibers in Thy1-EGFP mice reveals distinct morphological features of sensory and motor projections along the ventral and dorsal rami. Immunostaining facilitates body-wide mapping of sympathetic nerves and their branches, highlighting their perivascular patterns in limb muscles, bones, and most visceral organs. Viral tracing elucidates the fine architecture of vagus nerves and individual vagal fibers, revealing unexpected projection routes to various organs. Our approach offers an effective means to achieve a holistic understanding of cellular-level interactions among different systems that underlie body physiology and disease. HighlightsO_LIImaging of whole adult mouse at uniform subcellular resolution within 40 hours C_LIO_LIReconstruction of 191 thoracic spinal neuron projections for Thy1-EGFP mice C_LIO_LIMapping of immunolabeled sympathetic projections and their perivascular patterns C_LIO_LIResolving virus-labeled architecture of vagus nerves and complex single-fiber routes C_LI

neuroscience↗

bioRxiv2024

Aging drives a program of DNA methylation decay in plant organs

How organisms age is a question with broad implications for human health. In mammals, DNA methylation is a biomarker for biological age, which may predict age more accurately than date of birth. However, limitations in mammalian models make it difficult to identify mechanisms underpinning age-related DNA methylation changes. Here, we show that the short-lived model plant Arabidopsis thaliana exhibits a loss of epigenetic integrity during aging, causing heterochromatin DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging can be manipulated by extending or curtailing lifespan, and that shoot apical meristems are protected from this aging process. We demonstrate that a program of transcriptional repression suppresses DNA methylation maintenance pathways during aging, and that mutants of this mechanism display a complete absence of epigenetic decay. This presents a new paradigm in which a gene regulatory program sets the rate of epigenomic information loss during aging.

plant biology↗

bioRxiv2023

Effect of alpha-tubulin acetylation on the doublet microtubule structure

Acetylation of -tubulin at the lysine 40 residue (K40) by ATAT1/MEC-17 acetyltransferase modulates microtubule properties and occurs in most eukaryotic cells. Previous literatures suggest that acetylated microtubules are more stable and damage-resistant. K40 acetylation is the only known microtubule luminal post-translational modification site. The luminal location suggests that the modification tunes the lateral interaction of protofilaments inside the microtubule. In this study, we examined the effect of tubulin acetylation on the doublet microtubule in the cilia of Tetrahymena thermophila using a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry. We found that K40 acetylation exerts a small-scale effect on the doublet microtubule structure and stability by influencing the lateral rotational angle. In addition, comparative mass spectrometry revealed a link between K40 acetylation and phosphorylation in cilia.

cell biology↗

bioRxiv2023

Multi-omics of the gut microbial ecosystem in the immunotherapy resistance in microsatellite instability-high gastrointestinal cancer patients

Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogated gut microbiome, blood metabolome and cytokines/chemokines of MSI-H/dMMR advanced gastrointestinal cancer patients (N=77) and identified a number of microbes (e.g. Alistipes putredinis) and metabolites (e.g. arginine and SCFA) highly associated with primary resistance. Fecal microbiota transplantation of patients stool replicated the clinical responsiveness as well as certain molecular signatures. Based on the clinical microbiome data, we developed a predictive machine learning model for primary resistance and achieved accuracy at 0.83 on an external validation set. Furthermore, several microbes were pinpointed which gradually changed during the process of acquired resistance. In summary, our study demonstrated the essential role of gut microbiome in drug resistance, and this could be utilized as a preventative diagnosis tool as well as therapeutic targets in the future.

cancer biology↗

bioRxiv2023

Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis

Targeting the 4{beta}7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune system. Transcriptomic studies with protein level validation were used to study drug MOA using conventional and transgenic murine models. We found a significant decrease in colonic and ileal naive B and T cells and circulating gut-homing plasmablasts ({beta}7+) in VDZ-treated patients, pointing to gut-associated lymphoid tissue (GALT) targeting by VDZ. Murine Peyers patches (PP) demonstrated a significant loss cellularity associated with reduction in follicular B cells, including a unique population of epithelium-associated B cells, following anti-4{beta}7 antibody (mAb) administration. Photoconvertible (KikGR) mice unequivocally demonstrated impaired cellular entry into PPs in anti-4{beta}7 mAb treated mice. In VDZ-treated, but not anti-tumor necrosis factor-treated UC patients, lymphoid aggregate size was significantly reduced in treatment responders compared to non-responders, with an independent validation cohort further confirming these data. GALT targeting represents a novel MOA of 4{beta}7-targeted therapies, with major implications for this therapeutic paradigm in UC, and for the development of new therapeutic strategies.

immunology↗

bioRxiv2022

Dynamic DNA methylation turnover in gene bodies is associated with enhanced gene expression plasticity

BackgroundIn several eukaryotes, DNA methylation occurs within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance has remained unclear. ResultsWe report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages spanning over 100 million years, indicating evolutionary conservation. We demonstrate that Dynamic GbM is tightly associated with the presence of a promoter or regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. We find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity. Dynamic GbM genes exhibit reduced dynamic range in drdd mutants, indicating a causal link between DNA demethylation and enhanced gene expression plasticity. ConclusionsThis study proposes a new model for GbM in regulating gene expression plasticity, including a newly discovered type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state.

genomics↗

bioRxiv2022

Hyaluronic acid biosynthesis promotes an invasive, stem-like cancer cell phenotype by broadly altering metabolism

Metastasis is the leading cause of breast cancer-related deaths and often driven by invasion and cancer-stem like cells (CSCs). Both the CSC phenotype and invasion have been associated with increased hyaluronic acid (HA) production. How these independent observations are connected, and which role metabolism plays in this process remains unclear due in part to the lack of convergent approaches that integrate engineered model systems, computational tools, and cancer biology. Using microfluidic invasion models, metabolomics, computational flux balance analysis (FBA), and bioinformatic analysis of patient data we investigated the functional links between the stem-like, invasive, and metabolic phenotype of breast cancer cells as a function of HA biosynthesis. Our results suggest that CSCs are more invasive than non-CSCs and that broad metabolic changes caused by overproduction of HA play a role in this process. Accordingly, overexpression of hyaluronic acid synthases (HAS) 2 or 3 induced a metabolic phenotype that promoted breast cancer cell stemness and invasion in vitro and upregulated a transcriptomic signature that was predictive of increased invasion and worse survival in patients. Collectively, this study suggests that HA overproduction leads to metabolic adaptations that help satisfy the energy demands necessary for 3D invasion of breast cancer stem cells further highlighting the importance of engineered model systems and multidisciplinary approaches in cancer research.

cancer biology↗