The Notch Signaling Pathway Contributes to Angiogenesis and Tumor Immunity in Breast Cancer

Abstract

Nina Jiang,1,* Ye Hu,1,* Meiling Wang,2,* Zuowei Zhao,2 Man Li1 1Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Breast Surgery, the Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuowei Zhao, Department of Breast Surgery, the Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected] Man Li, Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Breast cancer in women is the first leading tumor in terms of incidence worldwide. Some subtypes of BC lack distinct molecular targets and exhibit therapeutic resistance; these patients have a poor prognosis. Thus, the search for new molecular targets is an ongoing challenge for BC therapy. The Notch signaling pathway is found in both vertebrates and invertebrates, and it is a highly conserved in the evolution of the species, controlling cellular fates such as death, proliferation, and differentiation. Numerous studies have shown that improper activation of Notch signaling may lead to excessive cell proliferation and cancer, with tumor-promoting and tumor-suppressive effects in various carcinomas. Thus, inhibitors of Notch signaling are actively being investigated for the treatment of various tumors. The role of Notch signaling in BC has been widely studied in recent years. There is a growing body of evidence suggesting that Notch signaling has a pro-oncogenic role in BC, and the tumor-promoting effect is largely a result of the diverse nature of tumor immunity. Immunological abnormality is also a factor involved in the pathogenesis of BC, suggesting that Notch signaling could be a target for BC immunotherapies. Furthermore, angiogenesis is essential for BC growth and metastasis, and the Notch signaling pathway has been implicated in angiogenesis, so studying the role of Notch signaling in BC angiogenesis will provide new prospects for the treatment of BC. We summarize the potential roles of the current Notch signaling pathway and its inhibitors in BC angiogenesis and the immune response in this review and describe the pharmacological targets of Notch signaling in BC, which may serve as a theoretical foundation for future research into exploring this pathway for novel BC therapies.Keywords: Notch signaling pathway, angiogenesis, tumor immunity, breast cancer, PD-1/PD-L1

Keywords

• notch signaling pathway
• angiogenesis
• tumor immunity
• breast cancer
• pd-1/pd-l1