ITK (IL2 Inducible T Cell Kinase)

Elevated mRNA levels of EMP3, THBS2, and ITGA5 were significantly correlated with poorer overall survival. Fn and Pg can promote invasive phenotypes in CRC through distinct mechanisms, each modulating a unique subset of p-EMT and without instigating a complete, coordinated EMT gene signature.

In confirmation of this, FN protein levels were higher in OSCC and BC tissues than in their normal counterparts. Given FN capability of favoring tumor invasion and metastasis while hindering antitumor immune responses, these data encourage the development of FN antagonists to be used as an adjunct to conventional therapy in the treatment of both OSCC and BC.

Moreover, we identified a gene cluster linked to cancer stem cell-like features, which may be clinically relevant for patient risk stratification. Overall, our findings underscore the complexity of EMT regulation in BC and introduce a new EMT signature with potential prognostic and therapeutic relevance.

To further understand the role of this kinase, we engineered a novel CAR incorporating an ITK-binding motif (PYRP), which enhances ITK recruitment, increases Y218 phosphorylation, and boosts IL-2 secretion, and improves anti-tumor efficacy in vivo . Our findings underscore the functional relevance of Y218 phosphorylation in modulating CAR-T cell fate and reveal a strategy to fine-tune CAR signaling through targeted kinase recruitment to enhance therapeutic efficacy.

EBV-associated smooth muscle tumors are more likely to occur in children or young adults with immune deficiency, often manifesting as multifocal lesions in different organs. Accurate diagnosis relies on a comprehensive assessment incorporating clinical history, histopathological features, and findings of immunohistochemistry and EBERs in situ hybridization.

Of these EMT-associated coTFs, PATZ1 was validated as a novel direct interactor of DNp73β. (4) Our results provide a comprehensive reference map of p73 isoform-specific binding and coregulator recruitment and establish a workflow to model their influence on cancer reprogramming with implications for AI-based individualized therapy.

Importantly, inhibition of ATR in tumors undergoing EMT reduces tumor growth and metastasis, suggesting that ATR inhibition eliminates cancer cells in transition. Thus, during EMT, ATR not only protects genome integrity but also enables transcription reprogramming, revealing that ATR is a safeguard of cell-state transitions and a target to suppress tumor plasticity.

However, no review has comprehensively addressed the cardiovascular toxicity of TFKs inhibitors. This review provides a comprehensive and systematic analysis of the cardiovascular toxicity profiles of TFK inhibitors (TFKis), focusing on underlying molecular mechanisms, comparing toxicity across different agents and generations, and discussing clinical implications.

In contrast, co-treatment with Cu and copper ionophore elesclomol (Cu-ES) triggered cuproptosis, a unique copper-dependent form of cell death, accompanied by mitochondrial dysfunction, dihydrolipoamide S-acetyltransferase aggregation, and ATP depletion. The PLK1 inhibitor BI-2536 recapitulated the effects of Cu-ES and exhibited synergistic activity when combined with Cu-ES, enhancing both cell death and EMT suppression. These findings highlight a novel regulatory mechanism of EMT through copper signaling and support copper-based combination therapies as a promising approach to simultaneously inhibit tumor growth and metastasis in colorectal cancer.

In contrast, RepID depletion resulted in a marked upregulation of GATA6 expression due to the loss of these repressive modifications. Collectively, these findings establish RepID as a pivotal upstream regulator of osteosarcoma metastasis through modulation of the PRC1-GATA6 axis, and highlight its potential as a promising therapeutic target.

Importantly, western blot analysis confirmed that 9 reduced phosphorylation of ITK (Tyr551/Tyr511) and downstream extracellular signal-regulated kinase 1/2 (ERK1/2) (Thr202/Tyr204) in phytohemagglutinin-stimulated Jurkat cells, supporting on-target inhibition of ITK signaling. These results position 9 as a selective ITK inhibitor with a favorable therapeutic index, establishing a foundation for further optimization and preclinical development.

S. epidermidis affects EMT gene expression and cell viability, indicating potential involvement in breast cancer progression.