Semaphorin 4C accelerates disease progression and enables disease detection in breast cancer

Abstract

Semaphorins constitute a diverse family of widely expressed transmembrane, diffusible, and GPI-linked proteins with versatile physiologic functions in orchestrating nerve system development, immune homeostasis, angiogenesis, and cell metabolism. Accumulating evidence highlights semaphorins as essential regulators of tumorigenesis by coordinating the cell-cell communications in the tumor microenvironment. Semaphorin 4C (SEMA4C) is a member of the fourth class of semaphorins with high affinity to Plexin-B2 and its interplay with cancer has long been a significant knowledge gap. Here, this perspective summarizes the recent progress in the understanding of SEMA4C in cancer and comprehensively delineates the discovery of SEMA4C in lymphatic vessels of breast cancer, the mechanisms by which SEMA4C promotes the invasiveness, proliferation, metastasis, and drug resistance of breast cancer, and the explorations of leveraging serum SEMA4C in breast cancer detection, highlighting SEMA4C as a critical driver of breast cancer progression, an effective biomarker for breast cancer diagnosis, and potential therapeutic target for breast cancer treatment.