Therapeutic targeting of ITGA1 delayed retinoblastoma progression through suppression of STAT3 signaling

Abstract

Retinoblastoma (Rb) is a malignant tumor of the retina that predominantly affects children, representing the most common primary intraocular malignancy in this population. Accumulating evidence implicates integrins as critical regulators of cancer progression. The present study aims to investigate the functional roles and therapeutic potential of ITGA1 in Rb pathogenesis. Bioinformatics analysis of the GSE224022 dataset identified 2813 upregulated and 2682 downregulated genes in Rb tissues, with pronounced enrichment in cell adhesion processes and integrin-mediated signaling pathways. Notably, ITGA1 and its binding partner ITGB1 exhibited marked overexpression in both Rb specimens and Y79 cells. Lentiviral-mediated ITGA1 knockdown or pharmacological inhibition with obtustatin significantly impaired the proliferation, migration, and clonogenicity of Y79 cells. Subsequent transcriptome analysis and western blot assays identified STAT3 as a key downstream mediator of ITGA1-mediated signaling pathways. Notably, treatment with ML115, a STAT3 agonist, partially rescued the inhibitory effects of ITGA1 suppression on Y79 cell proliferation and migration. In vivo studies using a murine xenograft model confirmed that ITGA1 knockdown substantially delayed tumor growth. Collectively, these findings suggest that targeting ITGA1 may represent a promising therapeutic strategy for Rb treatment.