Perspective Article

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

¹ Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan 430030, China
² National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan 430030, China
³ Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China

^* Corresponding authors: qingleigao@hotmail.com; zhf152@163.com

Received: 14 February 2023
Accepted: 6 May 2023

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.