SWAP70 undergoes dynamic conformational regulation at the leading edge of migrating cells

Kriplani, Nisha; Duncan, Rory R.; Leslie, Nicholas

doi:10.1002/1873-3468.13326

Cited by 8 publications

(4 citation statements)

References 50 publications

(88 reference statements)

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“…SLC2A10 regulated fibroblasts in arterial tortuosity syndrome by encoding glucose transporter 10 ( 41 ). The PI3K-dependent recruitment of SWAP70 to the plasma membrane has been observed in growth factor-stimulated fibroblasts ( 42 ). EMP3 plays an important role in the regulation of membrane receptors associated with IDH-Wild type glioblastoma ( 43 ).…”

Section: Discussionmentioning

confidence: 98%

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

et al. 2023

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BackgroundCancer-associated fibroblasts (CAFs) are vital components of prominent cellular components in lower-grade gliomas (LGGs) that contribute to LGGs’ progression, treatment resistance, and immunosuppression. Epigenetic modification and immunity have significant implications for tumorigenesis and development.MethodsWe combined aberrant methylation and CAFs abundances to build a prognostic model and the impact on the biological properties of LGGs. Grouping based on the median CAFs abundances score of samples in the TCGA-LGGs dataset, differentially expressed genes and aberrantly methylated genes were combined for subsequent analysis.ResultsWe identified five differentially methylated and expressed genes (LAT32, SWAP70, GSAP, EMP3, and SLC2A10) and established a prognostic gene signature validated in the CGGA-LGGs dataset. Immunohistochemistry (IHC) and in vitro tests were performed to verify these expressions. The high-risk group increased in tumor-promoting immune cells and tumor mutational burden. Notably, risk stratification had different ICB sensitivities in LGGs, and there were also significant sensitivity differences for temozolomide and the other three novel chemotherapeutic agents.ConclusionOur study reveals characteristics of CAFs in LGGs, refines the direct link between epigenetics and tumor stroma, and might provide clinical implications for guiding tailored anti-CAFs therapy in combination with immunotherapy for LGGs patients.

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Section: Discussionmentioning

confidence: 98%

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

et al. 2023

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“…Intravital measurements of FRET are achieved by either ratiometric measurements of donor and acceptor signals, by measuring the sensitized emission of the acceptor, or by measuring the donor's fluorescence lifetime (FLIM) (Piston and Kremers 2007;Jalink 2013;Conway et al 2014;Martin et al 2018). Cell motility can be studied using for example FRET-reporters for RhoA (Nobis et al 2017), Rac (Johnsson et al 2014;Yukinaga et al 2014), Src (Nobis et al 2013a;Vennin et al 2017), SWAP70 (Kriplani et al 2019), Arf6 (Hall et al 2008), or FAK (Seong et al 2013) activity.…”

Section: Ivm Of Fluorescent Properties To Reveal Molecular Eventsmentioning

confidence: 99%

Cellular Plasticity during Metastasis: New Insights Provided by Intravital Microscopy

Margarido

Bornes

Vennin

et al. 2019

Cold Spring Harb Perspect Med

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Metastasis is a highly dynamic process during which cancer and microenvironmental cells undergo a cascade of events required for efficient dissemination throughout the body. During the metastatic cascade, tumor cells can change their state and behavior, a phenomenon commonly defined as cellular plasticity. To monitor cellular plasticity during metastasis, high-resolution intravital microscopy (IVM) techniques have been developed and allow us to visualize individual cells by repeated imaging in animal models. In this review, we summarize the latest technological advancements in the field of IVM and how they have been applied to monitor metastatic events. In particular, we highlight how longitudinal imaging in native tissues can provide new insights into the plastic physiological and developmental processes that are hijacked by cancer cells during metastasis.

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“…SWAP-70 has been described as a unique F-actin regulatory protein, which binds and bundles F-actin (25), and has several non-redundant functions in various hematopoietic cells such as polarization (26), endocytosis (27), integrin-mediated adhesion (28,29), migration (30), and homing (26). In many of these cell types, it was observed that SWAP-70 localizes to sites of active F-actin rearrangement (31)(32)(33)(34)(35)(36). Swap-70 -/mice exhibit an osteopetrotic phenotype, characterized by increased bone mineral density caused by decreased resorptive activity of osteoclasts defective in F-actin ring formation (31,35).…”

Section: Introductionmentioning

confidence: 99%

Role of Dynamic Actin Cytoskeleton Remodeling in Foxp3+ Regulatory T Cell Development and Function: Implications for Osteoclastogenesis

et al. 2022

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In T cells, processes such as migration and immunological synapse formation are accompanied by the dynamic reorganization of the actin cytoskeleton, which has been suggested to be mediated by regulators of RhoGTPases and by F-actin bundlers. SWAP-70 controls F-actin dynamics in various immune cells, but its role in T cell development and function has remained incompletely understood. CD4+ regulatory T (Treg) cells expressing the transcription factor Foxp3 employ diverse mechanisms to suppress innate and adaptive immunity, which is critical for maintaining immune homeostasis and self-tolerance. Here, we propose Swap-70 as a novel member of the Foxp3-dependent canonical Treg cell signature. We show that Swap-70-/- mice have increased numbers of Foxp3+ Treg cells with an effector/memory-like phenotype that exhibit impaired suppressor function in vitro, but maintain overall immune homeostasis in vivo. Upon formation of an immunological synapse with antigen presenting cells in vitro, cytosolic SWAP-70 protein is selectively recruited to the interface in Treg cells. In this context, Swap-70-/- Treg cells fail to downregulate CD80/CD86 on osteoclast precursor cells by trans-endocytosis and to efficiently suppress osteoclastogenesis and osteoclast function. These data provide first evidence for a crucial role of SWAP-70 in Treg cell biology and further highlight the important non-immune function of Foxp3+ Treg cells in bone homeostasis mediated through direct SWAP-70-dependent mechanisms.

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SWAP70 undergoes dynamic conformational regulation at the leading edge of migrating cells

Cited by 8 publications

References 50 publications

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

Cellular Plasticity during Metastasis: New Insights Provided by Intravital Microscopy

Role of Dynamic Actin Cytoskeleton Remodeling in Foxp3+ Regulatory T Cell Development and Function: Implications for Osteoclastogenesis

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