GAS6 (Growth arrest specific 6)

Notably, over 80% of genes upregulated in ZFTA-RELAfus tumors were downregulated following MERTK inhibition, indicating a strong dependency on this pathway for tumor maintenance. These findings define a signaling vulnerability in ZFTA-RELA-driven ependymomas and support the clinical development of MERTK-targeted therapies for patients with the high-risk EPN-E1 subtype.

We established an efferocytosis-related prognostic signature and elucidated its underlying mechanism wherein MAGEA11 promoted immunosuppression via a Gas6-MERTK/AXL-dependent efferocytosis circuit. This integrated study positions efferocytosis as a key driver of the OS microenvironment and a promising target for clinical intervention.

Rescue experiments confirmed that wild-type GAS6, but not the truncated variant, restored cellular function. These findings establish GAS6 as a critical regulator of neuro-glial homeostasis and identify its deficiency as the cause of a previously unreported childhood-onset demyelinating disease.

The multiple mechanisms leading to the exclusion of relevant immune cells needed for an anti-cancer response and mechanisms leading to active immune suppression are part of complex cell-cell crosstalk. This study provides a deeper insight into the immune exhausted phenotype in CCA.

Our findings indicate that hMENA overexpression in CAFs defines a myofibroblast-like subset predominantly driven by TGF-β signaling, which sustains TGF-β1-mediated crosstalk between cancer cells and CAFs and impairs T-cell functionality. In NSCLC tissues, hMENAhigh CAFs associate with TGF-β and regulatory T-cell signatures and correlate with poor patient prognosis and resistance to immune checkpoint therapies, supporting their role as key contributors to an immunosuppressive, ICT-refractory tumor microenvironment.

Both SAXS and cryo-EM confirmed successful complex formation between the three proteins, and a low-resolution 3D model for the tilvestamab-AXL complex is presented. The data allow for sample optimization for high-resolution structural biology, as well as designing mutations that could alter binding affinity and specificity.

Combination therapy synergistically downregulated EGFR (0.41- vs. 0.74-fold warfarin, P0.05). The warfarin-bevacizumab combination synergistically impaired PDAC progression via multi-tiered EGFR-PI3K-Akt suppression and mitochondrial apoptosis activation, providing a rationale for clinical translation against oncogenic pathway plasticity.

SB431542 potentiates doxorubicin-induced apoptosis in TP53-mutant breast cancer cells by upregulating TAp63 and activating caspase-dependent pathways. These findings suggest that targeting the TGF-β/TAp63 signaling axis may offer a novel therapeutic approach to overcome chemoresistance in aggressive, TP53-mutant breast cancers.

Our findings unveil a sophisticated spatial paradigm of liver regeneration following radiation injury, wherein spatially partitioned hepatocyte subpopulations deploy compartmentalized repair programs to balance proliferative efficiency and metabolic adaptation, suggesting potential new targets for therapeutic intervention against RILI.

Drug sensitivity analyses further suggested that vandetanib may have the potential to inhibit recurrence by targeting B2M-related pathways. These findings provide evidence that B2M may contribute to remodeling of the immune microenvironment in recurrent HCC. Our integrative single-cell multi-omics approach highlights a possible mechanism of early recurrence and offers a preliminary predictive tool with therapeutic implications.

Gas6 Lips combined with AAV2-BEST1-hMERTK effectively preserved retinal structure and function in RCS rats and demonstrated long-term safety in primates, supporting its potential for clinical translation. This can provide preclinical efficacy and safety data for the clinical translation of Gas6 Lips for the treatment of retinal pigmentosa (RP).

Crucially, in vivo experiments demonstrate that this nanoplatform not only eradicates primary tumor sites but also effectively eliminates early metastatic lesions, leading to significant suppression of lung metastasis in an NPC model. This work establishes a strategic foundation for the rational design of nanotherapeutics that exploit cuproptosis for the treatment of aggressive and metastatic cancers.