Anoikis and NETosis in colorectal cancer liver metastasis: the relationship and perspectives

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with metastatic spread being the primary reason for fatalities. Anoikis, a form of programmed cell death triggered by cell detachment from the extracellular matrix (ECM), and NETosis, a neutrophil cell death mode releasing extracellular traps (NETs), play critical roles in CRC liver metastasis (CRCLM). This review explores the mechanisms of anoikis and NETosis, their interplay, and genetic underpinnings in CRCLM. Anoikis resistance in CRC cells allows survival during metastasis in the initial stage, while NETs promote tumor progression by facilitating immune evasion, ECM remodeling, and angiogenesis. Meanwhile, through bioinformatics analysis and summary, we elaborated on the relationship between anoikis and NETosis as well as the potential interaction mechanisms, exploring the connecting links between them. The crosstalk between these processes is analyzed, highlighting shared signaling pathways (e.g., PI3K/AKT, MAPK, EMT) and potential biomarkers (e.g., MUC13, GLI2, SIRT6, FASN). Therapeutic strategies targeting anoikis and NETosis, including inhibitors of integrins, EGFR, and NET components (e.g., DNase I, CXCR2 antagonists), inhibitors of autophagy (e.g., CQ, HCQ, azithromycin) are discussed. This comprehensive analysis advances understanding of CRCLM pathogenesis and provides novel perspectives for targeted interventions.