三阴性乳腺癌恶性程度高，易在病程早期转移，是目前临床治疗的难点，但调控三阴性乳腺癌转移的机制尚不明确。筑丝蛋白家族成员Tektin4参与微管稳定，其在肿瘤中的研究甚少，仅有一篇申请人以第一作者撰写的论文（Nat Commun, 2014）报道，Tektin4结构变异引起三阴性乳腺癌紫杉醇耐药。本项目前期结果显示：Tektin4低表达降低细胞微管稳定性，促进三阴性乳腺癌发生上皮-间质转化及侵袭转移，并提示患者更高的转移风险。因此我们假设：Tektin4低表达通过降低微管稳定性，易化肿瘤细胞上皮-间质转化，最终促进三阴性乳腺癌的侵袭转移。本项目中，我们将以“Tektin4-微管-上皮-间质转化-侵袭转移”为线索，利用本中心原发-转移灶配对标本及小鼠移植瘤模型，系统研究Tektin4在三阴性乳腺癌侵袭转移中的作用，探索微管稳定性下降易化上皮-间质转化的机制，为三阴性乳腺癌预后和治疗提供新线索。

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and has a high risk of early metastasis. However, the regulatory mechanism of TNBC metastasis is still unclear. Tektin4 is a member of the Tektin family which participates in microtubule stability, but little else is known regarding this protein. Our previous study (Nat Commun, 2014) showing that the structural variation of Tektin4 causes paclitaxel resistance in TNBC, was the only research to date regarding the role of Tektin4 in cancer. Our preliminary results showed that low expression of Tektin4 decreased cytoskeleton stability, promoting epithelial-mesenchymal transition (EMT) and enhancing the invasion ability of TNBC cells. Therefore, we hypothesized that the low expression of Tektin4 could reduce the stability of microtubules and promote EMT of tumor cells, eventually resulting in the invasion and metastasis of TNBC. In this project, we will use "Tektin4-microtubule-EMT-invasion and metastasis" as our main clue to systematically investigate the role of Tektin4 in the invasion and metastasis of TNBC, as well as the relationship between the decrease of microtubule stability and EMT. Paired primary and metastatic tumor samples and mouse xenograft models will greatly facilitate our research. The ultimate goal of our study is to develop new strategies to treat TNBC.