YAP1 (Yes associated protein 1)

Combination therapy with AF and αPD1 triggers a CD8+T cell-dependent antitumor immune response, thereby controlling tumor growth in situ or subcutaneously. In summary, our study reveals a PKCι-mediated immunosuppressive pathway driving ICIs resistance and support PKCι inhibition as a promising strategy to enhance immunotherapy efficacy in NSCLC.

No specific clustering was seen among different fusion types or tumor grade. Our findings support that BSS represents a unique and molecularly distinct sinonasal sarcoma with a characteristic DNA methylation signature, independent of gene fusion partners or histologic progression, providing a valuable tool for the classification of challenging cases.

These findings establish NRG4 as a metastasis suppressor in obesity-associated breast cancer by inhibiting the ERBB4-YAP1 pathway and down-regulating matrix metalloproteinases. Our study highlights the therapeutic potential of targeting NRG4-ERBB4 signaling to mitigate obesity-driven breast cancer progression.

Targeting the ECM-mediated autophagy regulation reduces autophagic heterogeneity, alters PDA growth, and shapes antitumor responses to FDA-approved therapies. In summary, we have characterized a non-metabolic regulation of autophagy through ECM sensing, opening the possibility to investigate and target ECM-specific outputs in diseases.

Gracillin, a natural compound, was identified as a CCL24 inhibitor and synergized with 5-fluorouracil and programmed cell death 1 monoclonal antibody therapies in allograft-bearing mice. CCL24 facilitates recruitment of CCR3+ TAMs, enhancing the immunosuppressive TME in CRC. Targeting CCL24 with agents like gracillin represents a promising therapeutic strategy.

Protein phosphatase 4 catalytic subunit (PPP4C) was found to interact with MST4 and reduce its function, thus promoting growth and immunosuppression in NSCLC by activating YAP1. This study demonstrates that PPP4C-mediated MST4 degradation contributes to growth activity and immunosuppression in NSCLC by restoring YAP1 activity, suggesting PPP4C and MST4 as potential targets for NSCLC management.

Accordingly, molecular analysis of the cases revealed the presence of an in-frame YAP1::MAML2 fusion transcript. To conclude, our cases confirmed that YAP1 fusions are the oncogenic drivers of a subset of adnexal tumors that may harbor poroid, follicular but also sebaceous differentiation.

Furthermore, under sorbitol-induced stress conditions-mimicking selected features of the bladder urothelium-MED15 forms stress-inducible, protein condensates and exhibits increased colocalization with YAP1. Collectively, these findings uncover a previously unrecognized MED15-TRIM11-YAP1 regulatory axis and support a model in which stress-induced MED15 condensates are associated with YAP1 stabilization and pro-metastatic behavior in bladder cancer.

Findings corroborate the idea of a mechanistic role for YAP1 in neuroblastoma adrenergic to mesenchymal reprogramming and therapy resistance. The YAP1-mediated plastic switch towards a mesenchymal expression state in neuroblastoma cells may provide the molecular basis for novel therapeutic avenues.

This proteome-wide MR and colocalization study identifies novel plasma proteins and immune pathways implicated in RTI susceptibility, providing insights into potential biomarkers and therapeutic targets for infection prevention and management. Further validation in diverse populations and tissue-specific proteomic studies is warranted.

These efforts identified MRK-A, a highly potent and selective lead compound with significantly improved cross-species pharmacokinetics and solubility compared to early leads. MRK-A demonstrated a robust PKPD relationship via selective, dose-dependent modulation of TEAD-driven genes and achieved complete tumor growth inhibition in the mesothelioma NCI-H226 xenograft mouse model with no observed adverse events.