蛋白激酶B
化学
PI3K/AKT/mTOR通路
细胞生物学
转移
整合素连接激酶
信号转导
癌症研究
癌细胞
细胞粘附
肌动蛋白细胞骨架
细胞迁移
适体
激酶
沃特曼宁
细胞
癌症
细胞骨架
生物
蛋白激酶A
生物化学
分子生物学
细胞周期蛋白依赖激酶2
遗传学
作者
Yong Wei,Shiyi Long,Min Zhao,Jing Zhao,Yun Zhang,He Wang,Limin Xiang,Jie Tan,Mao Ye,Weihong Tan,Yanbing Yang,Quan Yuan
摘要
Tumor invasion and metastasis are the main causes of tumor progression and are the leading causes of death among cancer patients. In the present study, we propose a strategy to regulate cellular signaling with a tumor metastasis-relevant cytoskeleton-associated protein 4 (CKAP4) specific aptamer for the achievement of tumor metastasis inhibition. The designed aptamer could specifically bind to CKAP4 in the cell membranes and cytoplasm to block the internalization and recycling of α5β1 integrin, resulting in the disruption of the fibronectin-dependent cell adhesion and the weakening of the cell traction force. Moreover, the aptamer is able to impede the interaction between CKAP4 and Dickkopf1 (DKK1) to further block the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which subsequently reduces AKT phosphorylation and inhibits the reorganization of the actin cytoskeleton in cell migration. The synergetic function of the designed aptamer in inhibiting cancer cell adhesion and blocking the PI3K signaling pathway enables efficient tumor cell metastasis suppression. The aptamer with specific targeting ability in regulating cellular signaling paves the way for cancer treatment and further provides a guiding ideology for inhibiting tumor metastasis.
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