最新研究表明前列腺癌（PCa）细胞骨转移关键过程与造血干细胞（HSC）向骨髓成骨细胞壁龛归巢相似，并与HSC竞争该壁龛且定植，但调控这一关键过程的机制还不十分清楚。HSC归巢受p53调控，而我们发现：p53是调控PCa骨转移的重要因素；p53靶微小145通过调节PCa细胞EMT及干性调控骨转移，且在p53调控转移过程中发挥重要作用；p53也了抑制CXCR4等下游效应分子表达。但p53是否是调控PCa细胞与HSC竞争成骨细胞壁龛的关键因素及调控机制仍待阐明。本项目通过观察p53不同水平对PCa细胞向成骨细胞迁移、粘附的能力及竞争性向成骨细胞壁龛归巢能力的影响；验证p53靶微小对其功能的介导作用；并探寻受p53或靶微小RNA调节且在PCa细胞竞争成骨细胞壁龛过程中发挥关键作用的分子，阐明p53对PCa骨转移细胞竞争成骨细胞壁龛的调控作用及机制，为探寻PCa骨转移预防和治疗的新靶标提供重要依据。

The primary cause of the death of prostate cancer (PCa) patients is the bone metastasis of tumor cells. Recent researches revealed that the critical process of bone metastasis of PCa resembled that of hematopoietic stem cells (HSCs), which is so-called "homing" to bone marrow niche that is essentially consisting of osteoblasts. PCa cells competed with HSCs to implant at niche and finally formed bone metastasis. The process of HSCs homing to niche was under the control of p53 that played a key role in the bone metastasis of PCa, and p53-targeted miR-34a mediated the metastatic process. In previous study we found miR-145 repressed the bone metastasis of PCa cells via regulating EMT (PLoS One. 2011;6(5)), and in pretest we discovered miR-145 played important roles in p53-regulating metastasis. Moreover, p53 also suppressed expressions of down-stream factors e.g. CXCR4, but the mechanism of p53 modulating PCa cells competitively binding to osteoblast niche remained unknown. So, in this program we intend to: 1) Identify the influence of p53 at different expression levels imposed on the abilities of PCa cells competitively migrating and adhering to osteoblast in vitro, and competitively homing to osteoblast in vivo. 2) Testify the regulating abilities of miR-34a and miR-145 in the process. 3) Further explore the proteins regulated by p53 and p53-targeted miRNAs and critically functioned in the process of tumor cells competing for niches. Eventually, we want to clarify the mechanism that p53 regulated the bone-metastatic PCa cells competing bone marrow niche, thus providing important basis for studying the prevention and therapy of PCa bone metasis.