侵袭伪足是促进肿瘤细胞向邻近部位侵袭的重要细胞结构。因此了解肿瘤细胞侵袭伪足形成过程，并对此过程进行人为干预，对于抑制恶性肿瘤细胞侵袭及转移过程至关重要。Basigin(BSG)为重要的肿瘤相关分子，参与多种肿瘤细胞侵袭转移过程，其选择性剪切变异体(BSG-2)能使不具有侵袭力的乳腺上皮细胞发生转化并形成侵袭伪足。本项目拟对BSG选择性剪切变异体(BSG-2和BSG-3)在肿瘤细胞侵袭伪足形成中的作用及其作用机制进行研究。以BSG与Annexin II 、Integrin β1和CD44的相互作用为出发点，围绕RhoC/ROCK/LIMK/Cofilin信号通路，及BSG/CD44/Integrin β1/FAK/Src信号通路，分析BSG不同选择性剪切变异体在肿瘤细胞侵袭伪足形成中的交互作用及其作用机制，为将调节BSG前体mRNA选择性剪切过程作为肿瘤转移防治的新策略提供理论依据。

Invadopodia, F-actin-driven membrane protrusions with matrix metalloproteinase (MMPs) activity to degrade the extracellular matrix (ECM), promote tumor metastasis. Invadopodia are enriched in a variety of proteins, including cortactin, cofilin, Arp2/3, and N-WASp. Basigin (BSG), a highly glycosylated type I transmembrane protein, is concerned as a cancer-associated biomarker and serves as a target for cancer therapy. Through extensive pre-mRNA alternative splicing, a large number of BSG isoforms are generated including Basigin alternative splice variant 2 (BSG-2) and variant 3 (BSG-3). Recent study shows that upregulation of CD147 (BSG-2) in non-transformed breast epithelial cells is sufficient for induction of matrix degrading invadopodia-like structures and increases invasion ability of these cells. In this project, we will study the role of BSG alternative splice variants (BSG-2 and BSG-3) in invadopodia formation of epithelial tumor cells, and determine which BSG splicing isoform plays the main role in invadopodia formation. Furthermore, we will demonstrate that BSG, CD44 and Integrin β1 function in one complicated membrane protein complex, which regulates the transition between focal adhesions (FAs) and invadopodia formation. This study is focused on RhoC/ROCK/LIMK/Cofilin and BSG/CD44/Integrin β1/FAK/Src signal pathway. We will block RhoC/ROCK/LIMK/Cofilin signal pathway by using ROCK inhibitor (H-1152 and Y-27632) and LIMK siRNA, to determine whether BSG-2 and BSG-3 regulate actin-barbed end initiation and invadopodia formation through RhoC/ROCK/LIMK/Cofilin signal pathway. We will also knockdown CD44 in BSG re-expression epithelial tumor cells to observe CD44’s function in BSG-dependent invadopodia formation. In short, we will try to reveal the contribution of BSG pre-mRNA alternative splicing and its’ splicing isoforms switch in invadopodia formation and tumor progression, and provide a potential cancer therapeutic target.