Song Xuelian, Wei Changran, Li Xiangqi
Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China.
Department of The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Oncol. 2022 Mar 10;12:855609. doi: 10.3389/fonc.2022.855609. eCollection 2022.
Breast 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.
Paget'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.
This 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.
乳腺癌目前是女性癌症的主要病因，而骨是乳腺癌远处转移的主要部位。乳腺癌骨转移严重影响患者生活质量并增加死亡率。然而，乳腺癌骨转移的机制尚未完全明确。
佩吉特的“种子与土壤”假说促使专家们探索乳腺肿瘤中的表面标志物和受体与骨中各种生长因子之间的关系。相关的乳腺肿瘤标志物充当“种子”，适合肿瘤生存的骨微环境充当“土壤”。这些因素相互作用组成一个完整的系统，并形成反馈通路，加速各种细胞因子的产生，吸引乳腺癌细胞迁移至骨组织，这会使乳腺癌病情恶化并严重影响患者预后。这个过程是一个恶性循环。目前，有七条主要信号通路参与乳腺癌骨转移：骨保护素/核因子κB受体活化因子/核因子κB受体活化因子配体信号通路、转化生长因子-β信号通路、胰岛素样生长因子系统、磷脂酰肌醇-3激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白信号通路、Wnt信号通路和Hippo信号通路。此外，成纤维细胞生长因子-成纤维细胞生长因子受体信号通路、雄激素-雄激素受体/赖氨酸特异性去甲基化酶1-靶基因通路、Notch信号通路、Janus激酶-信号转导及转录激活因子信号通路和钙调神经磷酸酶/活化T细胞核因子1信号通路似乎也与乳腺癌骨转移有关。
本综述聚焦于与乳腺癌骨转移相关的信号通路，并探讨这些通路之间的相互作用，这将为进一步理解乳腺癌骨转移机制及开发有效的靶向治疗药物奠定坚实的理论基础。
