Primary cilia connect epithelial mesenchymal plasticity with anoikis resistance and cancer stemness.

Metastatic dissemination requires carcinoma cells to coordinate reversible changes in epithelial identity with survival following extracellular matrix detachment and retention of tumor-initiating capacity. However, the mechanisms integrating epithelial-mesenchymal plasticity (EMP), anoikis resistance, and cancer stemness remain incompletely defined. Primary cilia are spatially restricted signaling compartments whose assembly and function vary with cell state, tumor lineage, and pathway context. This review evaluates how primary cilia may connect these metastatic adaptations by organizing responses to microenvironmental cues. Evidence from mammary epithelial and breast cancer models links selected EMP states to increased ciliogenesis and to Hedgehog-GLI or cilium-dependent GLIS2 signaling, which may support stem-like properties and treatment resistance. Ciliary signaling can also intersect with adhesion, cytoskeletal, and pro-survival pathways involved in survival after detachment. However, these downstream networks are not specific to primary cilia, and direct evidence that ciliary signaling causes anoikis resistance remains limited. Hypoxia, matrix stiffness, and receptor-mediated signals may further modify ciliary function and cellular plasticity, but their effects are tumor- and model-dependent. Overall, primary cilia should be viewed as context-dependent organizers rather than universal drivers of metastatic behavior. Future studies should define ciliary status alongside EMP state, anchorage-independent survival, and functional stemness to determine when cilia constrain tumor progression, support malignant signaling, or provide therapeutically actionable dependencies.