ITGAV (Integrin Subunit Alpha V)

Our study demonstrated that ITGAV can be used as an effective prognostic and immunological biomarker for multiple cancers. ITGAV can promote GC malignant progression and could serve as a potential therapeutic target for GC treatment.

(6) Molecular docking identified strong binding affinities between ITGAV and six candidate compounds, including gemcitabine and pioglitazone. Our findings demonstrate that ITGAV is a promising biomarker for diagnosis, prognosis, and immunotherapy prediction across cancers. Its immunological associations and druggability highlight its potential as a candidate therapeutic target.

Thus, ITGAV contributes to different patterns of PDAC progression. These findings suggest that stratifying PDAC patients based on both SMAD4 status and ITGAV expression could inform more effective integrin-targeted treatment strategies.

It also strengthens the adhesive features of senescent cells, increasing their binding to fibronectin via ITGAV, which may be a part of the phenotypic mode of drug resistance or slow interaction of proliferating cancer cells with the extracellular matrix (ECM). Thus, targeting senescent cells by focal adhesion modulators may be a promising approach to control drug-resistant melanoma cells.

The LGALS3BP-JUNB axis regulates ITGAV expression and contributes to HCC progression. Targeting ITGAV, with LGALS3BP as a potential biomarker, and the combined inhibition of both LGALS3BP and ITGAV may represent a promising therapeutic strategy for HCC.

After demonstrating that KBU2046 inhibits human ESCC metastasis in a murine model, we showed that it doesn't inhibit the in vitro efficacy of chemotherapeutic agents used clinically, going on to demonstrate maintenance of cisplatin efficacy when combined with KBU2046 in a murine model...Integrin αV (ITGAV) is overexpressed in ESCC, was decreased by KBU2046, and its knockdown inhibited ESCC cell migration and invasion, which was necessary for KBU2046 efficacy. We demonstrate that ESCC's motility can be inhibited, and KBU2046 inhibits motility in an Integrin αV-dependent manner, and that combining anti-motility and cytotoxic agents is a high value therapeutic strategy for ESCC that should be further developed.

Finally, immunoassays showed a significant correlation between ITGAV expression and the infiltration level of various immune cells, further clarifying the critical role of ITGAV in the tumor immune microenvironment. Our results elucidated the importance of ITGAV in the prognostic assessment, early diagnosis, and targeted immunotherapy of digestive system cancers, and revealed its multifaceted role in regulating cancer progression.

Taken together, these findings contribute to our understanding of GCIP in tumorigenesis and identify a previously unrecognized function of GCIP: It can interact with c-Myc and SIRT6 at E-box binding sites of the ITGAV promoter region. Our data collectively reveal a regulatory network involving GCIP, SIRT6, c-Myc, and ITGAV, and suggest that the SIRT6-GCIP complex negatively regulates the oncogenic function of c-Myc in cell proliferation and migration.

Our results demonstrate that ITGAV is a prognostic biomarker of relapse in cSCCs that would allow improved patient stratification. ITGAV also collaborates with IGF1R to induce EMP in epithelial cancer cells and promotes cSCC progression, revealing a potential therapeutic strategy to block the generation of advanced mesenchymal cSCCs.

Notably, OSMR fostered the expression of a distinct set of integrin genes, which in turn resulted into a crosstalk between OSMR and integrins for signaling activation that is critical for cisplatin resistance. Therefore, targeting OSMR emerges as a promising and viable strategy to reverse cisplatin-resistance in ovarian cancer.

The expression of ITGAV was associated with PNI and advanced disease, whereas the expression of CX3CL1 was related to TB, suggesting that ITGAV and CX3CL1 are involved in their respective developments. Therefore, further investigations are encouraged to assess the potential utility of targeted therapies against CX3CL1 receptors in OSCC.

No significant abnormalities were observed in the main organs of mice. Targeting the integrinαv on the surface of cancer cells could destroy extracellular matrix, improve drug delivery, and increase immune infiltration.