乳腺癌是全球发病率最高的肿瘤类型之一。无论是何种类型的乳腺癌，转移是导致恶性预后的关键原因。缺乏与原生环境相连的细胞死亡（一种称为离环死）是转移的外因内行过程，其始于整合素-细胞外基质（ECM）和钙粘蛋白-细胞等胞质连接器的破裂。该破裂之后会导致胞内细胞骨架和信号通路的变化，最终激活半胱氨酸蛋白酶并引发程序性细胞死亡。发展出离环死抵抗性表型是肿瘤转移的关键初始步骤。乳腺癌利用一系列基质反应以抑制肿瘤细胞的离环死。全面研究离环死抵抗机制，可为预防和逆转乳腺癌转移提供策略。本综述首先阐述了离环死的生理机制，阐明了正常乳腺细胞粘附丧失后由体外向体内发生的信号通路、细胞骨架和蛋白靶点的变化。此外，还讨论了乳腺癌发展过程中各种空间结构的病理改变引起的特定离环死抵抗机制。此外，总结了乳腺癌在离环死抵抗发展中的靶点基因位点。最后，综合了文献报道的与离环死相关的微小RNA和靶向药物，其中角蛋白是功能上最全面的。视频摘要。©2023. BioMed Central Ltd. Springer Nature的一部分。

Breast cancer exhibits the highest global incidence among all tumor types. Regardless of the type of breast cancer, metastasis is a crucial cause of poor prognosis. Anoikis, a form of apoptosis initiated by cell detachment from the native environment, is an outside-in process commencing with the disruption of cytosolic connectors such as integrin-ECM and cadherin-cell. This disruption subsequently leads to intracellular cytoskeletal and signaling pathway alterations, ultimately activating caspases and initiating programmed cell death. Development of an anoikis-resistant phenotype is a critical initial step in tumor metastasis. Breast cancer employs a series of stromal alterations to suppress anoikis in cancer cells. Comprehensive investigation of anoikis resistance mechanisms can inform strategies for preventing and regressing metastatic breast cancer. The present review first outlines the physiological mechanisms of anoikis, elucidating the alterations in signaling pathways, cytoskeleton, and protein targets that transpire from the outside in upon adhesion loss in normal breast cells. The specific anoikis resistance mechanisms induced by pathological changes in various spatial structures during breast cancer development are also discussed. Additionally, the genetic loci of targets altered in the development of anoikis resistance in breast cancer, are summarized. Finally, the micro-RNAs and targeted drugs reported in the literature concerning anoikis are compiled, with keratocin being the most functionally comprehensive. Video Abstract.© 2023. BioMed Central Ltd., part of Springer Nature.