Cell-in-cell (CIC) structures, characterized by one cell engulfing another, play a paradoxical role in cancer metastasis. This review synthesizes their dual nature: while CIC can suppress metastasis by eliminating aberrant cells or activating immune responses, it also drives tumor progression through clonal evolution, metabolic adaptation, and genomic instability. The clinical relevance of CIC varies across cancer types, correlating with both favorable and poor prognoses depending on disease stage and microenvironmental context. Emerging therapeutic strategies aim to harness protective CIC mechanisms or inhibit pro-metastatic pathways, though challenges such as biomarker validation and dynamic tracking persist. Future research integrating advanced technologies will elucidate the spatiotemporal complexity of CIC, enabling tailored interventions to disrupt metastatic cascades. By bridging fundamental biology and clinical translation, CIC represents a promising yet intricate frontier in the battle against metastatic cancer.
Cao et al. (Fri,) studied this question.