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Artificial intelligence (AI) use in diabetes care is increasingly being explored to personalise care for people with diabetes and adapt treatments for complex presentations. However, the rapid advancement of AI also introduces challenges such as potential biases, ethical considerations, and implementation challenges in ensuring that its deployment is equitable. Ensuring inclusive and ethical developments of AI technology can empower both health-care providers and people with diabetes in managing the condition. In this Review, we explore and summarise the current and future prospects of AI across the diabetes care continuum, from enhancing screening and diagnosis to optimising treatment and predicting and managing complications.
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Inteligencia Artificial , Diabetes Mellitus , Humanos , Inteligencia Artificial/tendencias , Diabetes Mellitus/terapia , Diabetes Mellitus/diagnósticoRESUMEN
Three-dimensional (3D) cellular assemblies, such as cancer spheroids and organoids, are increasingly valued for their physiological relevance, and versatility in biological applications. Nanopatterns that mimic the extracellular matrix provide crucial topological cues, creating a physiologically relevant cellular environment and guiding cellular behaviors. However, the high cost and complex, time-consuming nature of the nanofabrication process have limited the widespread adoption of nanopatterns in diverse biological applications. In this study, we present a straightforward and cost-effective elastomer replica molding method utilizing commercially available optical discs to generate various nanopatterns, such as nanogroove/ridge, nanoposts, and nanopits, varying in spacing and heights. Using the nanopatterned well chips (NW-Chips), we demonstrated the efficient formation of 3D multicellular self-assemblies of three different types of cancer cells. Our findings highlight the accessibility and affordability of optical discs as tools for nanopattern generation, offering promising avenues for modulating cell behaviors and advancing diverse biological applications.
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Nanoestructuras , Humanos , Nanoestructuras/química , Esferoides Celulares/citología , Línea Celular Tumoral , Propiedades de SuperficieRESUMEN
Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound environments. Here, we present a two-stage strategy using bioactive sucralfate-based microneedle (SUC-MN) for delivering interleukin-4 (IL-4) to accelerate wound healing. In the first stage, SUC-MN synergistically enhanced the effect of IL-4 through more potent reprogramming of pro-regenerative M2-like macrophages via the JAK-STAT pathway to increase endogenous GF production. In the second stage, sucralfate binds to GFs and sterically disfavors protease degradation to increase bioavailability of GFs. The IL-4/SUC-MN technology accelerated wound healing by 56.6 % and 46.5 % in diabetic mice wounds and porcine wounds compared to their respective untreated controls. Overall, our findings highlight the innovative use of molecular simulations to identify bioactive ingredients and their incorporation into microneedles for promoting wound healing through multiple synergistic mechanisms.
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Macrófagos , Agujas , Sucralfato , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Sucralfato/farmacología , Porcinos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Ratones Endogámicos C57BL , Diabetes Mellitus Experimental , Interleucina-4/metabolismo , Células RAW 264.7 , MasculinoRESUMEN
Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma.
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During cancer metastasis, cancer cells will encounter various microenvironments with diverse physical characteristics. Changes in these physical characteristics such as tension, stiffness, viscosity, compression, and fluid shear can generate biomechanical cues that affect cancer cells, dynamically influencing numerous pathophysiological mechanisms. For example, a dense extracellular matrix drives cancer cells to reorganize their cytoskeleton structures, facilitating confined migration, while this dense and restricted space also acts as a physical barrier that potentially results in nuclear rupture. Identifying these pathophysiological processes and understanding their underlying mechanobiological mechanisms can aid in the development of more effective therapeutics targeted to cancer metastasis. In this review, we outline the advances of engineering microfluidic devices in vitro and their role in replicating tumor microenvironment to mimic in vivo settings. We highlight the potential cellular mechanisms that mediate their ability to adapt to different microenvironments. Meanwhile, we also discuss some important mechanical cues that still remain challenging to replicate in current microfluidic devices in future direction. While much remains to be explored about cancer mechanobiology, we believe the developments of microfluidic devices will reveal how these physical cues impact the behaviors of cancer cells. It will be crucial in the understanding of cancer metastasis, and potentially contributing to better drug development and cancer therapy.
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Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structures are nearly identical. How other actin-binding proteins regulate ADP-actin filament assembly is unclear. Here, we show that Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast. Spa2 triggers ADP-actin monomer nucleation rapidly through a dimeric core of Spa2 (aa 281-535). Concurrently, the intrinsically disordered region (IDR, aa 1-281) guides Spa2 undergoing phase separation and wetting on the surface of ADP-G-actin-derived F-actin and bundles the filaments. Both ADP-actin-specific nucleation and bundling activities of Spa2 are actin D-loop dependent. The IDR and nucleation core of Spa2 are evolutionarily conserved by coexistence in the fungus kingdom, suggesting a universal adaptation mechanism in the fungal kingdom in response to glucose starvation, regulating ADP-G-actin and ADP-F-actin with high nucleotide homogeneity.
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Actinas , Adenosina Difosfato , Glucosa , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Difosfato/análogos & derivados , Glucosa/metabolismo , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/química , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/químicaRESUMEN
While the human gut microbiota has a significant impact on gut health and disease, understanding of the roles of gut microbes, interactions, and collective impact of gut microbes on various aspects of human gut health is limited by the lack of suitable in vitro model system that can accurately replicate gut-like environment and enable the close visualization on causal and mechanistic relationships between microbial constitutents and the gut. , In this study, we present a scalable Gut Microbiome-on-a-Chip (GMoC) with great imaging capability and scalability, providing a physiologically relevant dynamic gut-microbes interfaces. This chip features a reproducible 3D stratified gut epithelium derived from Caco-2 cells (µGut), mimicking key intestinal architecture, functions, and cellular complexity, providing a physiolocially relevant gut environment for microbes residing in the gut. Incorporating tumorigenic bacteria, enterotoxigenic Bacteroides fragilis (ETBF), into the GMoC enable the observation of pathogenic behaviors of ETBF, leading to µGut disruption and pro-tumorigenic signaling activations. Pre-treating the µGut with a beneficial gut microbe Lactobacillus spp., effectively prevent ETBF-mediated gut pathogenesis, preserving the healthy state of the µGut through competition-mediated colonization resistance. The GMoC holds potential as a valuable tool for exploring unknown roles of gut microbes in microbe-induced pathogenesis and microbe-based therapeutic development.
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Microbioma Gastrointestinal , Dispositivos Laboratorio en un Chip , Microbioma Gastrointestinal/fisiología , Humanos , Células CACO-2RESUMEN
To perform multiplex profiling of single cells and eliminate the risk of potential sample loss caused by centrifugation, we developed a microfluidic flow cytometry and mass spectrometry system (µCytoMS) to evaluate the drug uptake and induced protein expression at the single cell level. It involves a microfluidic chip for the alignment and purification of single cells followed by detection with laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). Biofunctionalized nanoprobes (BioNPs), conjugating â¼3000 6-FAM-Sgc8 aptamers on a single gold nanoparticle (AuNP) (Kd = 0.23 nM), were engineered to selectively bind with protein tyrosine kinase 7 (PTK7) on target cells. PTK7 expression induced by oxaliplatin (OXA) uptake was assayed with LIF, while ICP-MS measurement of 195Pt revealed OXA uptake of the drug in individual cells, which provided further in-depth information about the drug in relation to PTK7 expression. At an ultralow flow of â¼0.043 dyn/cm2 (20 µL/min), the chip facilitates the extremely fast focusing of BioNPs labeled single cells without the need for centrifugal purification. It ensures multiplex profiling of single cells at a throughput speed of 500 cells/min as compared to 40 cells/min in previous studies. Using a machine learning algorithm to initially profile drug uptake and marker expression in tumor cell lines, µCytoMS was able to perform in situ profiling of the PTK7 response to the OXA at single-cell resolution for tests done on clinical samples from 10 breast cancer patients. It offers great potential for multiplex single-cell phenotypic analysis and clinical diagnosis.
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Nanopartículas del Metal , Microfluídica , Humanos , Citometría de Flujo , Oro , Biomarcadores , Espectrometría de Masas/métodos , Moléculas de Adhesión Celular , Proteínas Tirosina Quinasas ReceptorasRESUMEN
Biological nanostructures change their shape and function in response to external stimuli, and significant efforts have been made to design artificial biomimicking devices operating on similar principles. In this work we demonstrate a programmable nanofluidic switch, driven by elastocapillarity, and based on nanochannels built from layered two-dimensional nanomaterials possessing atomically smooth surfaces and exceptional mechanical properties. We explore operational modes of the nanoswitch and develop a theoretical framework to explain the phenomenon. By predicting the switching-reversibility phase diagram-based on material, interfacial and wetting properties, as well as the geometry of the nanofluidic circuit-we rationally design switchable nano-capsules capable of enclosing zeptoliter volumes of liquid, as small as the volumes enclosed in viruses. The nanoswitch will find useful application as an active element in integrated nanofluidic circuitry and could be used to explore nanoconfined chemistry and biochemistry, or be incorporated into shape-programmable materials.
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Single-cell encapsulation in droplet microfluidics is commonly hindered by the tradeoff between cell suspension density and on-chip focusing performance. In this study, we introduce a novel droplet microfluidic chip to overcome this challenge. The chip comprises a double spiral focusing unit, a flow resistance-based sample enrichment module with fine-tunable outlets, and a crossflow droplet generation unit. Utilizing a low-density cell/bead suspension (2 × 106 objects/mL), cells/beads are focused into a near-equidistant linear arrangement within the double spiral microchannel. The excess water phase is diverted while cells/beads remain focused and sequentially encapsulated in individual droplets. Focusing performance was assessed through numerical simulations and experiments at three flow rates (40, 60, 80 µL/min), demonstrating successful focusing at 40 and 80 µL/min for beads and cells, respectively. In addition, both simulation and experimental results revealed that the flow resistance at the sample enrichment module is adjustable by punching different outlets, allowing over 50% of the aqueous phase to be removed. YOLOv8n-based droplet detection algorithms realized the counting of cells/beads in droplets, statistically demonstrating single-cell and bead encapsulation rates of 72.2% and 79.2%, respectively. All the results indicate that this on-chip sample enrichment approach can be further developed and employed as a critical component in single-cell encapsulation in water-in-oil droplets.
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The separation of specific cell populations is instrumental in gaining insights into cellular processes, elucidating disease mechanisms, and advancing applications in tissue engineering, regenerative medicine, diagnostics, and cell therapies. Microfluidic methods for cell separation have propelled the field forward, benefitting from miniaturization, advanced fabrication technologies, a profound understanding of fluid dynamics governing particle separation mechanisms, and a surge in interdisciplinary investigations focused on diverse applications. Cell separation methodologies can be categorized according to their underlying separation mechanisms. Passive microfluidic separation systems rely on channel structures and fluidic rheology, obviating the necessity for external force fields to facilitate label-free cell separation. These passive approaches offer a compelling combination of cost-effectiveness and scalability when compared to active methods that depend on external fields to manipulate cells. This review delves into the extensive utilization of passive microfluidic techniques for cell separation, encompassing various strategies such as filtration, sedimentation, adhesion-based techniques, pinched flow fractionation (PFF), deterministic lateral displacement (DLD), inertial microfluidics, hydrophoresis, viscoelastic microfluidics, and hybrid microfluidics. Besides, the review provides an in-depth discussion concerning cell types, separation markers, and the commercialization of these technologies. Subsequently, it outlines the current challenges faced in the field and presents a forward-looking perspective on potential future developments. This work hopes to aid in facilitating the dissemination of knowledge in cell separation, guiding future research, and informing practical applications across diverse scientific disciplines.
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Tratamiento Basado en Trasplante de Células y Tejidos , Filtración , Separación Celular , Dispositivos Laboratorio en un Chip , MicrofluídicaRESUMEN
Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. A powerful platform technology combining magneto-responsive hydrogel, cells, and wireless magneto-induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing. The hydrogel encapsulates U.S. Food and Drug Administration (FDA)-approved fibroblasts and keratinocytes to achieve â¼3-fold better wound closure in a diabetic mouse model. MDMS acts as a nongenetic mechano-rheostat to activate fibroblasts, resulting in â¼240% better proliferation, â¼220% more collagen deposition, and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto-responsive property also enables on-demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, a mechanosensitive fibroblast subpopulation is identified that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. The "all-in-one" system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.
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Diabetes Mellitus , Cicatrización de Heridas , Ratones , Animales , Diabetes Mellitus/terapia , Diabetes Mellitus/patología , Queratinocitos , Colágeno , Hidrogeles/farmacologíaRESUMEN
Transplanting human induced pluripotent stem cells (iPSCs)-derived spinal cord progenitor cells (SCPCs) is a promising approach to treat spinal cord injuries. However, stem cell therapies face challenges in cell survival, cell localization to the targeted site, and the control of cell differentiation. Here, we encapsulated SCPCs in thiol-modified hyaluronan-gelatin hydrogels and optimized scaffold mechanical properties and cell encapsulation density to promote cell viability and neuronal differentiation in vitro and in vivo. Different compositions of hyaluronan-gelatin hydrogels formulated by varying concentrations of poly(ethylene glycol) diacrylate were mechanically characterized by using atomic force microscopy. In vitro SCPC encapsulation study showed higher cell viability and proliferation with lower substrate Young's modulus (200 Pa vs 580 Pa) and cell density. Moreover, the soft hydrogels facilitated a higher degree of neuronal differentiation with extended filament structures in contrast to clumped cellular morphologies obtained in stiff hydrogels (p < 0.01). When transplanted in vivo, the optimized SCPC-encapsulated hydrogels resulted in higher cell survival and localization at the transplanted region as compared to cell delivery without hydrogel encapsulation at 2 weeks postimplantation within the rat spinal cord (p < 0.01). Notably, immunostaining demonstrated that the hydrogel-encapsulated SCPCs differentiated along the neuronal and oligodendroglial lineages in vivo. The lack of pluripotency and proliferation also supported the safety of the SCPC transplantation approach. Overall, the injectable hyaluronan-gelatin hydrogel shows promise in supporting the survival and neural differentiation of human SCPCs after transplantation into the spinal cord.
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Gingival connective tissue and its vasculature play a crucial role in the host's immune response against the periodontal microbiome and serve as a bridge between the oral and systemic environments. However, there is a lack of representative models that mimic the complex features of vascularized gingival connective tissue and its interaction with the periodontal microbiome, hindering our understanding of periodontal health and disease. Towards this pursuit, we present the characterization of vascularized gingival connective tissue equivalents (CTEs) as a model to study the interactions between oral biofilm colonizers and gingival tissues in healthy and diseased states. Whole-mount immunolabeling and label-free confocal reflectance microscopy of human fibrin-based matrix embedded with gingival fibroblasts and microvascular endothelial cells demonstrated the generation of bi-cellular vascularized gingival CTEs. Next, we investigated the response of the vascularized gingival CTEs to early, intermediate, and late oral biofilm colonizers. Despite colonization, the early colonizers did not elicit any significant change in the production of the cytokines and chemokines by the CTEs representative of the commensal and homeostatic state. In contrast, intermediate and late colonizers representing a transition to a diseased state exhibited connective tissue and vascular invasion, and elicited a differential immune response accompanied by increased monocyte migration. The culture supernatants produced by the vascularized gingival CTEs in response to early and intermediate colonizers polarized macrophages towards an immunomodulatory M2-like phenotype which activates and protects the host, while the late colonizers polarized towards a pro-inflammatory M1-like phenotype. Lastly,in silicoanalysis showed a high strength of associations between the proteins and transcripts investigated with periodontitis and vascular diseases. In conclusion, the vascularized gingival CTEs provide a biomimeticin vitroplatform to study host-microbiome interactions and innate immune response in periodontal health and diseased states, which potentially paves the way toward the development and assessment of novel periodontal therapeutics.
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Células Endoteliales , Periodontitis , Humanos , Células Endoteliales/metabolismo , Interacciones Microbiota-Huesped , Encía/metabolismo , Periodontitis/metabolismo , Tejido Conectivo/metabolismoRESUMEN
Cardiovascular diseases (CVDs) are a major cause of death worldwide, leading to increased medical care costs. To turn the scale, it is essential to acquire a more in-depth and comprehensive understanding of CVDs and thus formulate more efficient and reliable treatments. Over the last decade, tremendous effort has been made to develop microfluidic systems to recapitulate native cardiovascular environments because of their unique advantages over conventional 2D culture systems and animal models such as high reproductivity, physiological relevance, and good controllability. These novel microfluidic systems could be extensively adopted for natural organ simulation, disease modeling, drug screening, disease diagnosis and therapy. Here, a brief review of the innovative designs of microfluidic devices for CVDs research is presented, with specific discussions on material selection, critical physiological and physical considerations. In addition, we elaborate on various biomedical applications of these microfluidic systems such as blood-vessel-on-a-chip and heart-on-a-chip, which are conducive to the investigation of the underlying mechanisms of CVDs. This review also provides systematic guidance on the construction of next-generation microfluidic systems for the diagnosis and treatment of CVDs. Finally, the challenges and future directions in this field are highlighted and discussed.
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Enfermedades Cardiovasculares , Animales , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Sistemas Microfisiológicos , Microfluídica , Dispositivos Laboratorio en un Chip , CorazónRESUMEN
Novel haptics technologies are urgently needed to bridge the gap between entirely physical world and fully digital environment to render a more realistic and immersive human-computer interaction. Current virtual reality (VR) haptic gloves either deliver limited haptic feedback or are bulky and heavy. The authors develop a haptic glove or HaptGlove, an untethered and lightweight pneumatic glove, that allows users to "physically" interact in a VR environment and enables both kinesthetic and cutaneous sensations naturally and realistically. Integrated with five pairs of haptic feedback modules and fiber sensors, HaptGlove provides variable stiffness force feedback and fingertip force and vibration feedback, allowing users to touch, press, grasp, squeeze, and pull various virtual objects and feel the dynamic haptic changes. Significant improvements in VR realism and immersion are observed in a user study with participants achieving 78.9% accuracy in sorting six virtual balls of different stiffnesses. Importantly, HaptGlove facilitates VR training, education, entertainment, and socialization in a reality-virtuality continuum.
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Interfaces Hápticas , Tecnología Háptica , Humanos , Retroalimentación , Interfaz Usuario-Computador , TactoRESUMEN
Cancer cells in secondary tumors are found to form metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, the role of deleterious mechanical stresses in this change of metastatic potential is unclear. Here, by forcing cancer cells to flow through small capillary-sized constrictions, it is demonstrated that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing-induced cell death. Transcriptomic profiling reveals up-regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy-resistant phenotype. These results highlight a potential link between the microenvironmental physical stresses and the enhanced malignancy of metastasizing cancer cells which may be utilized as a therapeutic strategy in preventing the metastatic spread of cancer cells.
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Resistencia a Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Fenotipo , Proliferación Celular , Microambiente TumoralRESUMEN
One advantage of a resistive sensor array (RSA) with shared rows (M) and shared columns (N) is the reduced number of wires from M × N + 1 to M + N which can greatly lessen the complexity and burden on wearable electronic systems. However, the drawback is the crosstalk current effect between adjacent elements, which will lead to high measurement error. Although several solutions have been reported, they mainly focus on RSAs with high resistance (≥100 Ω). There is a lack of research that addresses RSAs with resistor values below 100 Ω. Here, we introduce a new circuit design named the dynamic zero current method (DZCM) to further decrease the measurement error. From the low value RSA test with ideal resistors, the DZCM exhibits lower error than the zero potential method (ZPM). In the case of the error variation ratio of amplifier offset voltage, the DZCM has a 4%/mV (row) to 7%/mV (column) ratio, while the ZPM has an almost 25%/mV (row) to 45%/mV (column) ratio and it increases with array size.
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Rho GTPases regulate cell morphogenesis and motility under the tight control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). However, the underlying mechanism(s) that coordinate their spatiotemporal activities, whether separately or together, remain unclear. We show that a prometastatic RhoGAP, ARHGAP8/BPGAP1, binds to inactive Rac1 and localizes to lamellipodia. BPGAP1 recruits the RacGEF Vav1 under epidermal growth factor (EGF) stimulation and activates Rac1, leading to polarized cell motility, spreading, invadopodium formation, and cell extravasation and promotes cancer cell migration. Importantly, BPGAP1 down-regulates local RhoA activity, which influences Rac1 binding to BPGAP1 and its subsequent activation by Vav1. Our results highlight the importance of BPGAP1 in recruiting Vav1 and Rac1 to promote Rac1 activation for cell motility. BPGAP1 also serves to control the timing of Rac1 activation with RhoA inactivation via its RhoGAP activity. BPGAP1, therefore, acts as a dual-function scaffold that recruits Vav1 to activate Rac1 while inactivating RhoA to synchronize both Rho and Rac signaling in cell motility. As epidermal growth factor receptor (EGFR), Vav1, RhoA, Rac1, and BPGAP1 are all associated with cancer metastasis, BPGAP1 could provide a crucial checkpoint for the EGFR-BPGAP1-Vav1-Rac1-RhoA signaling axis for cancer intervention.