Liu Bin, Wu Qingqing, Xuan Zuodong, Zheng Zeyuan, Du Yifan, Sui Xiuyuan, Wu Haodong, Zhang Zeyi, Zhang Zhengying, Zhong Min, Zhao Yue, Sun Huimin, Shao Chen
School of Medicine, Xiamen University, Xiamen, China.
Department of Urology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Cancer Sci. 2025 Oct;116(10):2640-2648. doi: 10.1111/cas.70154. Epub 2025 Aug 5.
Among the numerous malignant behaviors of tumors, metastasis plays a critical role in contributing to poor prognosis. Anoikis is a distinct form of apoptosis induced when cells detach from the extracellular matrix (ECM) or adhere to an improper ECM. It is a physiological obstacle to tumor cell metastasis. Anoikis resistance is considered to be a critical initial step in cancer cell metastasis. However, the mechanism by which tumor cells develop anoikis resistance is still unclear, in which the focal adhesion signaling pathway plays an important role. This review first outlines the composition of focal adhesion (FAs) multi-protein signaling complexes and then discusses the following three aspects: integrin expression changes of tumor cells, intracellular oxidative stress response, and FAs multi-protein signaling complex members activating downstream survival signaling pathways. The specific mechanisms of focal adhesion signaling pathways in tumor cell anoikis resistance and molecular characteristics of the anoikis resistance state are reviewed.
在肿瘤的众多恶性行为中，转移在导致预后不良方面起着关键作用。失巢凋亡是细胞从细胞外基质（ECM）脱离或黏附于不适当的ECM时诱导产生的一种独特的细胞凋亡形式。它是肿瘤细胞转移的生理障碍。失巢凋亡抗性被认为是癌细胞转移的关键起始步骤。然而，肿瘤细胞产生失巢凋亡抗性的机制仍不清楚，其中黏着斑信号通路起着重要作用。本文综述首先概述了黏着斑（FAs）多蛋白信号复合物的组成，然后讨论以下三个方面：肿瘤细胞整合素表达变化、细胞内氧化应激反应以及FAs多蛋白信号复合物成员激活下游生存信号通路。综述了黏着斑信号通路在肿瘤细胞失巢凋亡抗性中的具体机制以及失巢凋亡抗性状态的分子特征。
