播散肿瘤细胞进入骨髓，与骨基质细胞长期稳定共存(休眠)，形成骨转移早期“niche”结构(以下统称“niche”)，是乳腺癌趋骨转移的关键，但其相关分子机制尚不清楚。我们前期研究发现Annexin II-Annexin IIR(AXII-AXIIR)连接体是“niche”中介导癌细胞与骨基质细胞间粘附的驱动力，并可能通过对PI3K/Akt信号通路先抑制后激活的调控机制，起到对癌细胞增殖侵袭能力先抑制后增强的作用，是“niche”中癌细胞休眠——再激活过程的关键。据此，我们提出了“AXII-AXIIR连接体调控PI3K/Akt通路在“niche”中发挥重要作用”的研究假说。本项目将以AXII-AXIIR连接体为基点，以PI3K/Akt通路相关信号分子及休眠/激活相关蛋白为核心，探索“niche”重要分子机制，为乳腺癌早期骨转移临床诊断、预后及疗效预测提供标志物以及治疗研究靶点。

Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions (Dormancy). The biology of this process, including the microenvironment niche and supporting pathways, is unclear. Our previous study found that Annexin II-Annexin IIR (AXII-AXIIR) connector is the driving force of adhesion between cancer cells and bone matrix cells in niche, which may regulate proliferation and invasion of tumor cells through PI3K/Akt signaling pathway by “inhibiting-enhancing” mechanism, and could play a key role in the process of dormancy-reactivation. Based on this, we put forward the hypothesis that the AXII-AXIIR connector plays an important role in the regulation of PI3K/Akt pathway in niche. This project will focus on the AXII-AXIIR connector, and explore the regulation mechanism of dormancy-reactivation through PI3K/Akt pathway in niche. Our study will illuminate the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.