MVP维持COL12A1表达激活Integrin β1/FAK/ERK通路促进胃癌侵袭转移的机制研究

侵袭转移是导致胃癌患者预后差的重要因素，而现有的靶向药物疗效有限，因此需寻找新的治疗靶点。申请人前期发现COL12A1能促进胃癌侵袭转移，与MVP蛋白相互结合；而MVP能维持COL12A1在细胞膜的表达，调控FAK和ERK磷酸化以及细胞浆溶酶体的活性，与Integrin β1和FAK相互结合。因此，申请人提出“MVP通过维持COL12A1表达而激活Integrin β1/FAK/ERK信号通路促进胃癌侵袭转移”的假说。本项目拟探讨：1、MVP通过促进再循环内体维持COL12A1表达；2、COL12A1增强Integrin β1和FAK相互作用激活ERK，诱导胃癌侵袭转移；3、探讨MVP和COL12A1联合阻断在抑制胃癌侵袭转移中的作用。从而明确MVP通过调控COL12A1激活Integrin β1/FAK/ERK信号通路而促进胃癌侵袭转移的作用机制，为胃癌治疗提供潜在的靶点和理论依据。

Invasion and metastasis are still important factors leading to poor prognosis of gastric cancer. Our previous studies indicated that COL12A1 promoted gastric cancer invasion and metastasis, and bound to MVP. MVP maintained COL12A1 protein expression, regulated FAK and ERK phosphorylation and the activity of cytoplasmic lysosomes, and bound to Integrin β1 and FAK. Therefore, we proposed a scientific hypothesis that “MVP activates the Integrin β1/FAK/ERK signaling pathway by maintaining the expression of COL12A1 to promote gastric cancer invasion and metastasis”. We intend to explore: 1. MVP maintains COL12A1 expression by promoting the recycling endosome of COL12A1; 2. COL12A1 activates ERK by enhancing the interaction between Integrin β1 and FAK, which results in gastric cancer invasion and metastasis; 3. Explore the anti-tumor effects of the combined blockade of MVP and COL12A1 in gastric cancer. In this way, we clarify that MVP promote gastric cancer invasion and metastasis by maintaining COL12A1 expression and activating Integrin β1/FAK/ERK pathway. These finding could provide potential targets and theoretical basis for gastric cancer treatment.