ADP-ribosylation factor (Arf)-GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 (ACAP1) has been reported to serve as an adaptor for clathrin coat complex playing a role in endocytic recycling and cellular migration. The potential role of ACAP1 in lung adenocarcinoma (LUAD) has not been yet completely defined. We performed the comprehensive analyses, including gene expression, survival analysis, genetic alteration, function enrichment, and immune characteristics. ACAP1 was remarkably downregulated in tumor tissues, and linked with the clinicopathologic features in LUAD patients. Prognostic analysis demonstrated that low ACAP1 expression was correlated with unsatisfactory overall survival (OS) and disease specific survival (DSS) in LUAD patients. Moreover, ACAP1 could be determined as a prognostic biomarker according to Cox proportional hazard model and nomogram model. We also confirmed that ACAP1 was downregulated in two LUAD cell lines, comparing to normal lung cell. Overexpression of ACAP1 caused a profound attenuation in cell proliferation, migration, invasion, and promoted cell apoptosis. Additionally, functional enrichment analyses confirmed that ACAP1 was highly correlated with T cell activation and immune response. Then, we further conducted immune landscape analyses, including single cell RNA sequencing, immune cells infiltration, and immune checkpoints. ACAP1 expression was positively associated with the infiltrating level of immune cells in TME and the expression of immune checkpoint molecules. This study first comprehensively analyzed molecular expression, clinical implication, and immune landscape features of ACAP1 in LUAD, suggesting that ACAP1 was predictive of prognosis and could serve as a potential biomarker predicting immunotherapy response for LUAD patients.

Members of the RAS proto-oncogene superfamily are indispensable molecular switches that play critical roles in cell proliferation, differentiation, and cell survival. Recent studies have attempted to prevent the interaction of RAS/GTP with RAS guanine nucleotide exchange factors (GEFs), impair RAS-effector interactions, and suppress RAS localization to prevent oncogenic signalling. The present study aimed to investigate the effect of the natural triterpenoic acid inhibitor glycyrrhetinic acid, which is isolated from the roots of Glycyrrhiza plant species, on RAS stability. We found that glycyrrhetinic acid may bind to the P-loop of RAS and alter its stability. Based on our biochemical tests and structural analysis results, glycyrrhetinic acid induced a conformational change in RAS. Meanwhile, glycyrrhetinic acid abolishes the function of RAS by interfering with the effector protein RAF kinase activation and RAS/MAPK signalling.

Cell chemotaxis plays a pivotal role in normal development, inflammatory response, injury repair and tissue regeneration in all organisms. It is also a critical contributor to cancer metastasis, altered angiogenesis and neurite growth in disease. The molecular mechanisms regulating chemotaxis are currently being identified and key components may be pertinent therapeutic targets. Although these components appear to be mostly common in various cells, there are important differences in chemotactic signaling networks and signal processing that result in the distinct chemotactic behavior of mesenchymal cells compared to much better studied amoeboid blood cells. These differences are not necessarily predetermined based on cell type, but are rather chosen and exploited by cells to modify their chemotactic behavior based on physical constraints and/or environmental conditions. This results in a specific type of chemotactic migration in mesenchymal cells that can be selectively targeted in disease. Here, we compare the chemotactic behavior, signaling and motility of mesenchymal and amoeboid cells. We suggest that the current model of chemotaxis is applicable for small amoeboid cells but needs to be reconsidered for large mesenchymal cells. We focus on new candidate regulatory molecules and feedback mechanisms that may account for mesenchymal cell type-specific chemotaxis.

Epithelial repair in the Drosophila embryo is achieved through 2 dynamic cytoskeletal machineries: a contractile actomyosin cable and actin-based cellular protrusions. Rho family small GTPases (Rho, Rac, and Cdc42) are cytoskeletal regulators that control both of these wound repair mechanisms. Cdc42 is necessary for cellular protrusions and, when absent, wounds are slow to repair and never completely close. Rac proteins accumulate at specific regions in the wound leading edge cells and Rac-deficient embryos exhibit slower repair kinetics. Mutants for both Rho1 and its effector Rok impair the ability of wounds to close by disrupting the leading-edge actin cable. Our studies highlight the importance of these proteins in wound repair and identify a downstream effector of Rho1 signaling in this process.

Repair of wounds to single cells involves dynamic membrane and cytoskeletal rearrangements necessary to seal the wound and repair the underlying cytoskeleton cortex. One group of proteins essential to the cortical remodeling is the Rho family of small GTPases. Recently we showed that the founding members of this GTPases family, Rho, Rac, and Cdc42, are all essential for normal single cell wound repair and accumulate at the wound periphery in distinct temporal/spatial patterns in the Drosophila cell wound model. In addition, these proteins communicate with one another and with the cytoskeleton to regulate their distribution in response to wounds. Unexpectedly, we found evidence for context specific Rho GTPase binding to downstream targets or \"effectors\" which cannot be explained solely by means of local GTPase activation. Here we discuss these observations in relation to similar studies in single cell wound repair in the Xenopus oocyte, and highlight how these cell wound models serve as powerful tools to understand both cell wound repair and Rho GTPase biology.