RHOA (Ras homolog family member A)

Furthermore, this platform supported large-scale, high-throughput-compatible expansion of aggressive cancer cells, offering a robust tool for CSC-focused studies and drug screening. Our findings highlight the utility of curvature-mediated mechanobiology in engineering more physiologically relevant and scalable in vitro cancer models.

Mechanistically, we show that ADGRG1 promotes preOL maturation by RhoA activation. Collectively, these findings reveal an ADGRG1-mediated RhoA signaling pathway that governs axon ensheathment and myelin formation.

In CAR T cells this results in more efficient targeting through decreased sampling time and increased engagement with carcinoma cells, consistent with modeling predictions. This significantly increases T cell infiltration and distribution in PDA, resulting in improved tumor control in vivo, suggesting that this is an effective strategy to overcome stromal constraints, improve tumor engagement, and enhance the therapeutic performance of engineered T cell therapies in solid tumors.

αPD-1 promotes ASCVD progression by enhancing macrophage inflammation and T-cell recruitment within plaques. RYR mitigates these effects through RhoA inhibition, suggesting its therapeutic potential for improving cardiovascular outcomes in ICIs-treated cancer patients with ASCVD.

Based on aMD simulations, we uncovered evidence of epistatic relationships between the Rho salt bridge, the distal residue K98 and P-loop residue D13 which coordinate allosteric communication from the switch regions directly to the active site. Finally, we describe the functional landscape of switch II pocket in the context of both Rho subfamily evolution and potential for drug discovery.

Mechanistically, we identify Ca2+/calmodulin-dependent protein kinase II (CaMKII) and tumor endothelial marker 4 (TEM4) as key mediators relaying the TRPV4-mediated Ca2+ signal to RhoA. These data define a molecular pathway by which Ca2+ influx regulates small GTPase activity within a specific cellular domain-lamellipodia-and demonstrate its critical role in organizing the actin machinery and promoting cell migration in diverse biological contexts.

Mechanistically, ARHGAP36, through the arginine-rich domain at the N-terminal, binds to β-catenin to stabilize P-cadherin expression in a way accompanying with, and mutually exclusive from, its interaction with PKAc to activate RhoA signaling. Thus, this study unveiled a heretofore unrecognized coordination mechanism for entosis, where ARHGAP36 engages both adherens junction and actomyosin to drive cell-in-cell formation, providing a promising cancer therapeutic target.

Extending to differentiation, integrin-ECM crosstalk directs lineage commitment across diverse fates, including hematopoietic, cardiovascular, neural, hepatic, epithelial, endodermal, and oligodendroglial lineages, by fine-tuning signaling specificity and ECM composition. This review focuses on recent advances in the mechanistic interplay between integrin signaling and ECM proteins in hPSC maintenance, mechanotransduction, and lineage-directed differentiation, emphasizing defined culture systems and their translational potential in regenerative medicine.

PCDH10 restoration antagonizes tumorigenesis by dual blockade of Wnt/β-catenin and Akt signaling pathways through interactions with GSK-3β, β-catenin, and LMNA, as a scaffold protein. Our findings reveal a novel PCDH10-dependent tumor-suppressive axis and highlight its potential as a therapeutic target and biomarker in breast cancer.

In vivo, mice injected with tumor cells pre-cultured on high-stiffness ECM-mimicking hydrogels exhibited accelerated subcutaneous tumor growth and increased lung metastatic burden, which were significantly attenuated by FAK-targeted therapy. These findings establish ECM stiffness as a biomechanical determinant of ATC progression and metastasis, offering novel insights into microenvironment-driven malignancy and highlighting FAK as a promising therapeutic target to disrupt mechanosignaling in ATC.

Critically, pharmacological inhibition abolished GGPPS-driven geranylgeranylation-dependent signaling: JSH-23 reversed both the proliferation mediated by RHOA and NF-κB p65 and the upregulation of IL1B potentiated by GGPS1 overexpression; and NSC23766 blocked the RAC1/STAT1-dependent IL1RAP activation amplified by GGPPS elevation, confirming that both axes are indispensable for GGPPS-dependent proliferation. Collectively, this GGPPS-mediated geranylgeranylation axis, converging on IL-1 pathway amplification, represents a central therapeutic vulnerability in LUSC, highlighting GGPPS as a promising macromolecular target for this recalcitrant malignancy.

This altered actin state led to an increase in BCR microcluster formation, amplification of NF-κB signaling, and resistance to inhibitors targeting chronic active BCR signaling. Hence, our study establishes RHOA and its mutant isoforms as critical regulators of oncogenic BCR signaling in DLBCL.