CD47 Contributes to the Proliferation of Breast Cancer.

Abstract

Background: The CD47 molecule (CD47) performs a novel role in regulating immunoreactions by binding to signal-regulatory protein alpha (SIRPα), resulting in the tumorigenesis of multiple malignant neoplasms. However, its effects and mechanisms in breast cancer (BC) remain unknown.

Methods: To explore the molecular mechanisms and explicit impacts of CD47, we screened two databases for CD47-associated signaling pathways and cellular functions. BC samples and patients' basic information were collected to identify the statistical significance of CD47 expression. We also constructed experiments to validate the regulatory role of CD47 in BC cell proliferation.

Results: Analysis of the TCGA-BRCA, GSE42568, and GSE15852 datasets demonstrated an elevated level of CD47 in BC tissues. A Venn diagram revealed 11,194 co-expressed genes, and pathway analysis linked elevated CD47 levels to critical signaling pathways, such as cytokine-receptor interactions and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, which are integral to cell proliferation and invasiveness. Clinical data from 108 BC specimens showed that CD47 localization was primarily membranous, with higher levels correlating with proliferation marker Ki-67 (Ki-67) expression (p < 0.0001) and advanced tumor/node/metastasis (TNM) stage (p < 0.0001). Additionally, functional assays demonstrated that CD47 depletion reduced cell viability (p < 0.01), migration (p < 0.001), and invasion (p < 0.05 in 4T1 cells; p < 0.001 in MDA-MB-231 cells) in vitro and led to smaller tumor volumes (p < 0.0001) in vivo.

Conclusion: CD47 is a key regulator of BC cell proliferation and invasiveness and serves as a potential marker for assessing tumor aggressiveness and guiding therapeutic strategies.