NAT1调控NF-κB/IL-1B信号通路促进Luminal型乳腺癌骨转移的机制研究

Bone is the main target organ of breast cancer metastasis. Luminal breast cancer has the highest incidence of bone metastasis. Currently, the treatment of breast cancer bone metastasis is difficult to make a qualitative change in clinical prognosis. Metastasis has become one of the main reasons for the failure of clinical treatment of breast cancer. Relevant studies have shown that continuous education of bone microenvironment before and after metastasis of cancer cells plays an important role in regulating bone metastasis. Previous studies found that NAT1 expression in Luminal breast cancer was significantly up-regulated and closely related to bone metastasis. The migration and colonization ability of tumor cells with high expression of NAT1 was enhanced. Moreover, NAT1 played an important role in regulating the differentiation of osteoblasts and osteoclasts. Protein chip assay indicated that NAT1 could regulate the expression of IL-1B through NF-kappa B signaling pathway, thereby affecting the above-mentioned process. However, intrinsic regulating mechanism and the role of IL-1B in the education of bone microenvironment remain unclear. Based on previous studies, we aimed to explore the molecular mechanism of NAT1/NF-kappa B/IL-1B signaling pathway regulating bone metastasis in Luminal breast cancer by using a series of in vivo and in vitro models. And to provide a new theoretical basis for searching for diagnostic markers of bone metastasis and targeted therapeutic drugs.

骨是乳腺癌转移的主要靶器官，Luminal型乳腺癌最容易发生骨转移。目前针对乳腺癌骨转移的治疗难以使患者的临床预后发生质的改变，转移已成为肿瘤临床治疗失败的主要原因之一。相关研究表明，肿瘤细胞转移前及转移后对骨微环境的持续改造，在调控肿瘤骨转移过程中发挥重要作用。课题组前期研究发现，Luminal型乳腺癌中NAT1表达明显上调，且与骨转移密切相关；高表达NAT1的肿瘤细胞迁移及定植能力增强，同时对成骨细胞及破骨细胞分化具有重要调控作用；蛋白芯片发现NAT1可以通过NF-κB信号通路调控IL-1B的表达，进而影响上述过程，但具体调控机制以及IL-1B在肿瘤细胞改造骨微环境中的作用尚不清楚。基于此，课题组拟通过体内、体外模型探索NAT1/NF-κB/IL-1B信号通路调控Luminal型乳腺癌骨转移的分子机制，为寻找肿瘤骨转移的诊断标记分子及靶向治疗药物提供新的理论依据。

骨是乳腺癌转移的主要靶器官，Luminal型乳腺癌最容易发生骨转移。目前针对乳腺癌骨转移的治疗难以使患者的临床预后发生质的改变，转移已成为肿瘤临床治疗失败的主要原因之一。相关研究表明，肿瘤细胞转移前及转移后对骨微环境的持续改造，在调控肿瘤骨转移过程中发挥重要作用。课题组研究发现，Luminal型乳腺癌中NAT1表达明显上调，且与骨转移密切相关；高表达NAT1的肿瘤细胞迁移及定植能力增强，同时对成骨细胞及破骨细胞分化具有重要调控作用；蛋白芯片发现NAT1可以通过NF-κB信号通路调控IL-1B的表达，进而影响上述过程。基于此，课题组通过体内、体外模型证明了NAT1/NF-κB/IL-1B信号通路调控Luminal型乳腺癌骨转移的分子机制，为寻找肿瘤骨转移的诊断标记分子及靶向治疗药物提供新的理论依据。