Abstract
BackgroundBreast cancer (BC) is now the leading cause of cancer in women, and bone is the primary site of distant BC metastasis. BC bone metastasis seriously affects the quality of life of patients and increases the mortality rate. However, the mechanism of BC bone metastasis is not fully understood.Main BodyPaget’s “seed and soil” hypothesis led experts to explore the relationship between surface markers and receptors in breast tumors and various growth factors in bone. The relevant breast tumor markers serve as “seeds”, and the bone microenvironment that is suitable for the survival of the tumor serves as the “soil”. These factors interact to make up an entire system and form feedback pathways that accelerate the production of various cytokines, attracting BC cells to migrate to bone tissue, which worsens the development of BC and seriously affects the prognosis of patients. This process is a vicious cycle. At present, there are seven major signaling pathways involved in BC bone metastasis: the OPG/RANK/RANKL signaling pathway, TGF-β signaling pathway, IGF system, PI3K-AKT-mTOR signaling pathway, Wnt signaling pathway and Hippo signaling pathway. In addition, FGF-FGFR signaling pathway, androgen-AR/LSD1-target gene pathway, Notch signaling pathway, JAK-STAT signaling pathway and CaN/NFATC1 signaling pathway also seem to be associated with BC bone metastasis.ConclusionThis review focuses on the signaling pathways related to BC bone metastasis and explores the interactions among these pathways, which will lay a solid theoretical foundation for further understanding the mechanism of BC bone metastasis and developing effective targeted therapeutic drugs.
Highlights
Breast cancer (BC) is the most common malignant tumor and the most important health burden, as well as the most common cause of cancer death among women worldwide
Metastatic bone disease is the result of the interaction between metastatic breast cancer (BC) cells and some cells in the bone microenvironment, which indicates that the prognosis is poor and seriously affects the quality of life of these patients
BC patients with bone metastasis are extremely susceptible to bone-related complications, known as skeletal-related events (SREs), including bone pain, hypercalcemia, pathological fractures, and spinal cord compression, are commonly used to assess the quality of life and status of patients with BC bone metastases [8]
Summary
Breast cancer (BC) is the leading cause of cancer in women, and bone is the primary site of distant BC metastasis. The relevant breast tumor markers serve as “seeds”, and the bone microenvironment that is suitable for the survival of the tumor serves as the “soil”. These factors interact to make up an entire system and form feedback pathways that accelerate the production of various cytokines, attracting BC cells to migrate to bone tissue, which worsens the development of BC and seriously affects the prognosis of patients. FGF-FGFR signaling pathway, androgen-AR/LSD1-target gene pathway, Notch signaling pathway, JAK-STAT signaling pathway and CaN/NFATC1 signaling pathway seem to be associated with BC bone metastasis
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