化学治疗是乳腺癌产生耐药及侵袭转移问题的重要原因。以潜在耐药靶标为基础，阐明其在耐药和侵袭转移中的作用机理，探索它在信号网络中的调控机制是目前研究的热点。前期我们已成功建立了人乳腺癌紫杉醇耐药细胞株，并发现Transgelin 2是乳腺癌耐药分子靶标，它过表达可下调PTEN激活PI3K/Akt通路；抑制Akt活性又可降低Transgelin 2表达，此外，该耐药细胞还有较强的侵袭转移能力，但Transgelin 2是否诱导该过程发生并未完全阐明。本项目是既往研究的深入，拟从细胞、裸鼠模型及临床样本三水平探讨Transgelin 2诱导乳腺癌侵袭转移的作用机制；并利用其与PI3K/PTEN/Akt通路的反馈作用，从转录、表观遗传和蛋白水平三方面阐明Transgelin 2在信号网络中的调控机制，明确其在乳腺癌化疗中辅助诊断耐药和侵袭转移的临床应用价值，为提高乳腺癌化疗疗效提供重要的科学依据。

Chemotherapy is an important reason of drug resistance, invasion and metastasis produced in breast cancer. Based on the potential drug-resistant target, it is becoming the popular issue of current research to elucidate its mechanism of resistance, invasion and metastasis in breast cancer and explore its regulatory mechanism in network of the signaling pathway. In previous study, we successfully established the paclitaxel-resistant human breast cancer cell line and found Transgelin 2 is the molecular target of the drug-resistant breast cancer, which overexpression could inhibit PTEN level by activating PI3K/Akt pathway, and inactivation of Akt could also suppress the expression of Transgelin 2. Moreover, the resistant cells possessed the strong ability of invasion and metastasis. But the mechanism that Transgelin 2 induces invasion and metastasis has not yet entirely illuminated in breast cancer. This project is in-depth study of previous work, we will investigate the mechanism of drug-resistant target Transgelin 2 inducing invasion and metastasis from in-vitro, in-vivo and clinical specimens. And we will illustrate regulatory mechanism of Transgelin 2 in the signaling pathway using the feedback effect between it and PI3K/PTEN/Akt pathway from transcription, epigenetics and protein levels. The clinical value of Transgelin 2 will be clarified in the auxiliary diagnosis of chemotherapy resistance, invasion and metastasis in breast cancer. These will provide important scientific basis for improving chemotherapeutic effect of breast cancer.