Cell Cannibalism Mechanisms in Tumor Biology

Cell cannibalism encompasses a spectrum of processes in which malignant cells engulf neighbouring cells, leading to diverse outcomes such as cell death, persistence or release of the internalised cell. The paradigm of entosis involves contractile forces mediated by RhoA and ROCK that drive live cell internalisation through cadherin-based adhesion. Variants include phagocytic uptake of apoptotic corpses, emperitosis of cytotoxic immune cells and macropinocytic capture of stromal elements. Following internalisation, lysosomal pathways—often involving LAMP1—degrade the engulfed cell, while in specific contexts the internalised cell can escape and re-enter the extracellular milieu. Heterotypic cannibalism of immune or stromal cells contributes to immune evasion, nutrient scavenging and metastatic dissemination. These cell-in-cell (CIC) events foster intratumoural heterogeneity, induce genomic instability and may influence epithelial–mesenchymal transition. Clinically, quantification of CIC structures correlates with prognosis across multiple cancers, and targeting the underlying signalling nodes offers novel avenues for therapeutic intervention.

Research from Nature Portfolio

Recent studies have revealed that entotic engulfment can exert pathogenic effects beyond cancer. In a developmental neurogenesis model, excessive entosis among progenitor cells led to prolonged mitosis and cortical thinning, effects reversible by ROCK inhibition. Foundational work on mutant p53 has shown that, unlike wild-type p53 hosts that perish upon engulfment, mutant p53 cells survive, displaying multinucleation, tripolar spindles and heightened genomic instability. In xenograft systems, co-cultures enriched for CIC events and p53 mutations demonstrated accelerated tumour growth and recurrence, underscoring the pro-tumorigenic potential of cell cannibalism in driving chromosomal heterogeneity.

Cell Cannibalism Mechanisms in Tumor Biology publication trend

The graph below shows the total number of articles in cell cannibalism mechanisms in tumor biology across all publications each year (not limited to Nature Index journals).

Technical terms

Entosis: A process of live cell internalisation driven by RhoA/ROCK-mediated contractility and cadherin-based adhesion.

Cell-in-cell (CIC) structure: A membrane-bound vacuole within a host cell containing one or more internalised cells.

RhoA/ROCK pathway: A signalling cascade regulating actomyosin contraction essential for the mechanical forces of entotic engulfment.

Mutant p53: A tumour suppressor gene variant that, when altered, enables host cell survival after entotic engulfment and promotes genomic instability.

LAMP1: Lysosomal-associated membrane protein 1, which facilitates acidification and degradation of internalised cells within CIC vacuoles.

References

1. An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis. Nature Communications (2023).
2. Entosis: the core mechanism and crosstalk with other cell death programs. Experimental & Molecular Medicine (2024).
3. Loss of RND3/RHOE controls entosis through LAMP1 expression in hepatocellular carcinoma. Cell Death & Disease (2024).
4. Mechanisms and significance of entosis for tumour growth and progression. Cell Death Discovery (2024).
5. Genomic instability in mutant p53 cancer cells upon entotic engulfment. Nature Communications (2018).
6. Rapid reuptake of granzyme B leads to emperitosis: an apoptotic cell-in-cell death of immune killer cells inside tumor cells. Cell Death & Disease (2013).