癌转移不仅是肿瘤恶化的标志，还是治疗失败与死亡的重要原因。目前肿瘤转移机理尚未明确。申请人前期研究发现1）乳腺癌转移组织中维甲酸受体β2（RARB2）低表达；2）非转移性乳腺癌细胞中RARB2高表达； 预实验发现非转移肿瘤细胞内RARB2功能缺失提高该细胞转移力，提示RARB2可抑制肿瘤转移，但作用机制亟待深入探索。在前期研究基础上，本项目以乳腺癌与肺癌考察对象通过分子、细胞、实验动物与临床手术标本分析RARB2基因在肿瘤转移中的临床意义、生物学功能、作用靶点及其分子机制。揭示RARB2基因在肿瘤转移中的抑制功能与机理，因此本研究将为阐明肿瘤转移研究提供新思路，研究的结果将为肿瘤转移治疗与新药筛选提供新手段和靶点。

Metastasis, the spread and growth of tumor cells to distant organs,represents the most devastating attribute of cancer, causes the majority ofcancer patient deaths. The molecular mechanisms of how the metastasis progress remains one of the most enigmatic aspectsof the disease. Our previous studies have shown that the transcription level of RARB2 is much lower in metastatic breast cancer samples than that in the primary breast cancer specimens. Furthermore, we have shown that the non-metastatic T47D breast cancer cells became invasive after functionally inactivating RARB2. All these indicate that RARB2 functions as a metastasis suppressor gene. However, the molecular mechanism ofRARB2 protecting against tumor metastasis is still unknown. Based on our preliminary results, we propose to investigate the potential key downstream genes or key signaling pathways of the RARB2 gene, which play central roles to inhibit tumor metastasis. To do these, we will molecularly dissect the cellular and mouse models, as well as human breast and lung cancer samples to define the molecular mechanism of RARB2's metastasis-inhibition effect. We expect that through performing the proposed studies,we may pinpoint the key genes or pathways etiologically involved in metastasis progression. Subsequently, functional inhibition of these target genes or pathwaysmay provide a novel strategy to prevent or treat breast and lung cancer patients.