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

## TL;DR

This study identifies key proteins that control B7-H3 expression in breast cancer stem cells, offering new targets for cancer therapy.

## Contribution

The study reveals novel transcription factors and a drug target for B7-H3 regulation in breast cancer stem cells.

## Key findings

- DDB1, XRCC5, PARP1, RPA1, and RPA3 are key regulators of B7-H3 in breast CSCs.
- Nitazoxanide reduces B7-H3 expression and CSC properties by inhibiting DDB1.
- The findings suggest new therapeutic strategies targeting B7-H3 regulation in cancer.

## Abstract

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 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 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.

•Key transcription factors of B7-H3 in breast CSCs are identified using DAP-MS•DDB1, XRCC5, PARP1, RPA1, and RPA3 regulate B7-H3 expression in breast CSCs•Nitazoxanide inhibits DDB1, reducing B7-H3 expression and CSC properties•Insights into B7-H3 regulation suggest new CSC-targeted therapeutic strategies

Key transcription factors of B7-H3 in breast CSCs are identified using DAP-MS

DDB1, XRCC5, PARP1, RPA1, and RPA3 regulate B7-H3 expression in breast CSCs

Nitazoxanide inhibits DDB1, reducing B7-H3 expression and CSC properties

Insights into B7-H3 regulation suggest new CSC-targeted therapeutic strategies

Molecular biology; Cell biology; Cancer; Omics.