VAV1 (Vav Guanine Nucleotide Exchange Factor 1)

Our findings suggest the existence of a Vav1/PDX1/miR-375/Akt axis as part of the complex network orchestrating the generation of functional β cells. These insights indicate that strategies aimed at specifically modulating Vav1 levels may positively impact the generation of IPCs in vitro and, ultimately, β cell replacement therapy for T1D.

Finally, we showed that VAV1 is necessary for the binding of GLI1 and its coactivator the histone acetyltransferase PCAF to this regulatory element. Taken together, our data supports a role for VAV1 in GLI1 transcriptional regulation, elucidating a new mechanism of function for nuclear VAV1 in PDAC cells.

Consistent with these functional improvements, this CAR construct induced robust phosphorylation of key activation pathways, including AKT, VAV1, ERK, PLCγ1, and NF-κB. The CAR construct incorporating the NKG2DTM-2B4-FCER1G is demonstrated to be the most effective in enhancing NK cell functionality.

Additionally, we demonstrated that these compounds inhibited growth of patient-derived organoids models of pancreatic cancer. These findings underscore the translational value of these cationic DAG-lactones for pancreatic cancer patients expressing Vav1 and serve as foundation for future approaches targeting atypical C1 domain-containing signaling proteins.

A significant finding is the elucidation of a non-canonical RT-loop degron (RDxS motif, residues 796-799) within VAV1 SH3 2 , distinct from previously characterized G-loop degrons. This discovery, supported by advanced computational modeling using the YDS-GlueFold platform and validated by site-directed mutagenesis, highlights versatility of CRBN in recognizing diverse neosubstrate motifs.

CD84 may mediate an immunosuppressive phenotype, facilitating immune evasion in breast cancer. This highlights its potential as a therapeutic target, particularly in triple-negative breast cancer, to overcome immune resistance and enhance treatment efficacy.

Gene expression signatures associated with late PDX passages (3rd-5th) were enriched with proliferation and metabolic reprogramming-related genes and predicted prognosis in an independent AITL series. Low PHLPP2 mRNA expression predicted poor prognosis (p = 0.05) and engineered PHLPP2 or TET2 loss in CD4+ T-cells showed enhanced PI(3)K activation, thus uncovering a therapeutic target for clinical trials.

Defining how KRAS mutants drive distinct outcomes in human pancreatic cancer is critical for developing allele-specific therapeutic approaches. This study unveils a hierarchy among KRAS G12D , KRAS G12V , and KRAS G12R to drive tumor initiation, owing to heterogeneous activation of EGFR, PI3K/AKT, and RAC1 signaling, thus revealing mutation-specific evolutionary paths in pancreatic tumorigenesis.

Additionally, several genetic alterations may have the potential to predict a response to a specific molecularly targeted agent, such as ALK fusions for ALK inhibitors, PD-L1 SVs for immune checkpoint inhibitors (including anti-PD-1 antibodies), and mutations in epigenetic regulators for histone deacetylase inhibitors and hypomethylating agents. In this study, we summarize the current understanding of somatic alterations in various subtypes of PTCLs and highlight their clinical utility.

It was found that autofluorescence attenuation parameters of NAD(P)H coenzyme in human glioblastoma cells change significantly when exposed to both YT-Vav1+CISH-/- and YT-Vav1+B2M-/-, indicating occurrence of an early metabolic shift in tumor cells towards a less aggressive oxidative phenotype, and this is consistent with dead cells fraction increase and living cells fraction decrease in spheroid composition. The data obtained on enhanced cytotoxic activity of new modified NK cell lines against human glioblastoma spheroids are important to understand interaction mechanisms between tumor and immune cells and the development of glioblastoma adoptive cell therapy.

With endogenous levels of SAP expression, 2B4-CAR-T cells exposed sufficient antitumor efficacy in vivo without excess cytokine production. Our results may help explain the biphasic feature of 2B4 in T cell responses from the viewpoint of the signalosome and provide a new candidate for CAR development.

Additionally, pristimerin significantly inhibited the migration and invasion of TNBC cells and enhanced the sensitivity of TNBC cells to doxorubicin. Collectively, this study provides the initial evidence that pristimerin directly targets HSPA8 to activate the VAV1/ERK pathway, thereby promoting cell autophagy and apoptosis.