Semaphorins: Novel Insights on Their Emerging Multifaceted Roles in the Evolving Landscape of Breast Cancer

Abstract Semaphorins, initially identified as phylogenetically conserved axon guidance molecules, comprise an extracellular signaling protein family involved in various biological events that regulate the development, tissue homeostasis and cancer progression of many organ systems. In recent years, the focus of research has expanded to investigate the roles of semaphorins in cancer. Semaphorins have emerged as crucial regulators in the pathogenesis of breast cancer (BCa). This review article aims to provide an overview of the contemporary knowledge regarding semaphorins, their diverse tumor-modulating properties, and their clinical application in BCa. Specifically, six semaphorins (SEMA3C, SEMA3E, SEMA4A, SEMA4C, SEMA4D, and SEMA7A) have been demonstrated to promote tumor progression in terms of BCa. Six additional members (SEMA3A, SEMA3B, SEMA3F, SEMA4B, SEMA6B, and SEMA6D) have been associated with tumor suppression. Several semaphorins (SEMA4C and SEMA7A) are considered putative diagnostic and prognostic biomarkers in BCa. Exploring and elucidating the intricate functions of semaphorins and their viability as therapeutic targets is an intriguing avenue of research that can improve BCa outcomes.