Unveiling transcriptional mechanisms of B7-H3 in breast cancer stem cells through proteomic approaches

Unveiling transcriptional mechanisms of B7-H3 in breast cancer stem cells through proteomic approaches

Blog Article

Summary: B7-H3, an immune checkpoint molecule, is prominently overexpressed in various solid tumors, correlating with poor clinical outcomes.Despite its critical role in promoting tumorigenesis, metastasis, and immune evasion, the regulatory mechanisms governing B7-H3 expression, particularly in cancer stem cells (CSCs), remain elusive.In this comprehensive Garden study, we focused on breast CSCs to uncover the transcriptional regulators driving B7-H3 overexpression.Utilizing DNA affinity purification-mass spectrometry (DAP-MS) to analyze B7-H3 promoter regions, we identified a novel set of transcription factors, including DDB1, XRCC5, PARP1, RPA1, and Rotary Blades RPA3, as key modulators of B7-H3 expression.Functional assays revealed that targeting DDB1 with nitazoxanide significantly downregulated B7-H3 expression, subsequently impairing tumor sphere formation and cell migration in breast CSCs.

These findings not only elucidate the complex transcriptional network controlling B7-H3 expression but also open new avenues for developing targeted immunotherapies aimed at disrupting CSC-driven cancer progression.