侵袭性伪足在乳腺癌转移中具有重要作用。Erk和Src可磷酸化侵袭性伪足的重要调节蛋白Cortactin，是调控侵袭性伪足的关键分子。我们前期的研究证实AIP1（GAPs蛋白家族新成员）可以通过Ras抑制Erk活性。近期我们的研究又发现：在转移性乳腺癌组织中AIP1的表达较非转移性乳腺癌显著减少；AIP1定位于侵袭性伪足，其PR结构域和Src的SH3可相互结合。因此推测：AIP1-Erk/Src-Cortactin共同参与侵袭性伪足的调节，抑制乳腺癌转移。本课题拟完成：1.在细胞水平探讨AIP1调节侵袭性伪足形成，抑制乳腺癌细胞转移的生物学功能。2.揭示AIP1调节Src/Erk的分子机制。3.以裸鼠乳腺癌转移模型和临床乳腺癌标本证实AIP1-Erk/Src-Cortactin通路调节侵袭性伪足的形成，从而抑制乳腺癌转移。本课题将为遏制乳腺癌转移提供可能的分子靶点。

Invadopodia plays an important role in breast cancer metastasis. Erk and Src, which could phosphorylate the novel regulatory protein Cortactin, are key proteins in regulating invadopodia. Our published paper has showed that AIP1-a new member of GAPs family (GTPase activating proteins), can inhibit the activity of Erk by regulating Ras,and our preliminary data indicates that the decrease of AIP1 was observed in the breast cancer with metastasis, compared to breast cancer without metastasis; AIP1 is Co-localized with F-actin in invadopodia, and its PR domain can bind to SH3 domain of Src. So, we speculate that AIP1-Erk/Src-Cortactin signal involves into invadopodia formation and inhibits metastasis in breast cancer. Our project will discuss the function of AIP1 in invadopodia formation and breast cancer metastasis,and uncover the mechanism of AIP1 regulating Erk/Src,verify that the AIP1-Erk/Src-Cortactin signal is responsible for inhibiting invadopodia formation and breast cancer metastasis in clinic breast cancer samples and the animal model of breast cancer metastasis of null mice.The project will give a possible molecular target for preventing breast cancer metastasis.