ITGB4 (Integrin Subunit Beta 4)

Our previous work established that the elevation of ITGB4 in BLCA was closely related to cisplatin resistance...Our research also discovered a positive correlation between ITGB4 and the ADCs drug target NECTIN4, and the overexpression of ITGB4 upregulates BLCA sensitivity to enfortumab vedotin treatment. It provides a basis for the treatment choice of advanced BLCA patients with immunotherapy resistance. Collectively, these results suggest that ITGB4 may be a promising therapeutic target for advanced BLCA.

Single-cell sequencing data showed that LUAD patients exhibited an immunosuppressive TME phenotype, which was exacerbated by high TIMP1 expression in epithelial cells, promoting Treg cell activity. The 7-gene ARG prognostic model established in this study shows promising potential as a clinically applicable tool for decision-making.

Suppression of proliferation with CDK4/6 inhibitor Palbociclib stimulated integrin β4 expression and induced protection against cisplatin in cells naturally expressing low levels of integrin β4. Our investigations reveal that expression of integrin β4 inversely correlates with cell cycle progression programs, whether observed in expression data of OC patient samples or in various OC cell lines. Consistently with these results, the overexpression of ITGB4 gene in ovarian cancer cell lines correlated with reduced cell proliferation rates and diminished sensitivity to cisplatin, supporting the idea that integrin β4 and likely its matrix ligands play critical roles in the regulation of cellular growth and chemoresistance of ovarian cancer cells.

Serial samples obtained from one leukemia cutis case throughout consecutive immune checkpoint blockade with ipilimumab followed by nivolumab showed a consistently high degree of overlap between local and circulating T cell receptor (TCR) sequences, suggesting that only a minority of eAML-associated T cells are leukemia-specific. Our analysis reveals eAML to associate with complex changes in leukemia and T cell gene expression profiles that suggest multiple potential avenues for therapeutic targeting.

In a previous publication, our group defined some of the mechanisms that vitamin D analogue paricalcitol (P) and hydroxychloroquine (H) potentiated the effects of gemcitabine-based chemotherapy in PDAC. Based on this, we hypothesized that PH may potentiate 5-fluorouracil (5FU) and Oxaliplatin-based chemotherapy, and this may involve a novel mechanism of extracellular matrix (ECM) modulation...We identified a new mechanism of action of PH through inhibiting ITGB4, leading to ECM modulation. These results suggest that the combination of PH with cytotoxic chemotherapy should be tested in PDAC clinical trials.

This study sheds light on the molecular mechanisms of gemcitabine resistance in iCCA, emphasizing lactylation's role and the significance of immune modulation. ITGB4 is identified as a promising therapeutic target, and the findings suggest that targeting these genes could help overcome resistance in iCCA.

This case broadens the reported urological spectrum of ITGB4-related JEB by illustrating a papillomatous-follicular bladder phenotype. Early urological evaluation in patients with JEB presenting with unexplained urinary symptoms may facilitate timely, targeted management and help prevent chronic complications.

The PD-L1/ITGB4 axis drives sorafenib resistance via FAK/AKT/mTOR hyperactivation. Dual targeting of PD-L1/ITGB4 enhances sorafenib efficacy, revealing a tumor-intrinsic mechanism and proposing a novel combinatorial strategy for HCC.

In addition, ITGB4 affects the expression of P-gp and the activity of antioxidant enzymes through the MAPK/NF-κB pathway, thereby promoting cisplatin efflux and chemoresistance. Our research uncovers a novel mechanism behind cisplatin resistance and indicates that USP44 could be a promising therapeutic target for overcoming cisplatin resistance in gastric cancer patients.

Biologically, MLN4924 effectively suppresses the migration and invasion of breast cancer cells in vitro and metastasis in vivo, which is largely rescued by ITGB4 overexpression. Taken together, our study revealed a new mechanism by which MLN4924 suppresses the migration and invasion of breast cancer cells by epigenetically inhibiting ITGB4 expression via enhancing H3K18 lactylation.

Intratumoral injection of AKOS (15, 30 mg/kg, every 5 days) effectively suppressed the tumor growth in HCT116 xenograft mouse models in vivo. Collectively, we demonstrate that AKOS is a promising chemical probe for targeting USP14 in CRC, offering a novel strategy for disrupting the malignant progression of CRC.

Our findings suggest that ncRNA-mediated ITGB1 expression is associated with poor prognosis and tumor-immune infiltration in GC. However, further validation through extensive mechanistic studies and large-scale clinical trials is warranted.