Figure 1
Phylogenetic tree of multicellularity and cell-in-cell phenomena. Adjusted using multicellularity data from19,20,21. We have highlighted in bold the line of how we found the position of each human gene in time from Vertebrates down to the closest common ancestor of all taxa shown in this phylogenetic tree. Made with NCBI Common Tree22, iTOL23 (version 6.7.4), and PhyloPic (phylopic.org) (version 2.0). Branch lengths show the approximate ages (MYA) of each branch from TimeTree. (A) AlyA plays a role in lysozyme activity; FspA is a possible receptor or regulator in the folate-sensing pathway. (B) SLC11A1 is involved in killing bacteria inside the cell. (C) FAT1 mediates cell–cell adhesion and can bind to β-catenin. (D) ACTB is involved in cell–cell adhesion; CDC42 downregulation controls phagocytosis and entosis; PRKAA1, PRKAB1,2, and PRKAG1,2,3 are involved in AMPK which is required for entosis; RAB7A is a phagocytic marker; LYST is involved in lysosome maturation. (E) TM9SF4 is associated with tumour cell cannibalism; CYBB is involved in killing bacteria inside the cell. (F) KRAS is an entotic marker. (G) CD163 is a macrophage marker involved in cell-in-cell phenomena; MSR1 is a macrophage marker. (H) CTSG regulates pathogen killing in neutrophils. (I) RHOA is involved in entosis and phagocytosis; DIAPH1 is involved in cell-tension pathways during entosis. (J) WASF1 is involved in phagosome maturation. (K) MYH1,2 and CTNNB1 are involved in cell–cell adhesion during entosis; ADGRE1 is a phagocytic marker; EZR is involved in cell cannibalism and heterotypic cell-in-cell phenomena; CTNNA2 is required for entosis; TP53: enhances engulfment processes; CD68 is a phagocytic and cannibalistic marker; LAMP1 is a phagolysosomic marker; CD36 mediates phagocytosis. (L) CDH1,2,3 are cell-in-cell and entotic markers. (M) SELL is involved in heterotypic cell-in-cell phenomena. (N) LYZ is a cannibalistic marker. (O) CD2 is involved in heterotypic cell-in-cell phenomena. (P) ICAM1 is involved in heterotypic cell-in-cell phenomena. Examples of conspecific killing (≥ 1 neoplastic cell) include entosis, cannibalism, and the host cell not always being an immune cell. Examples of conspecific cell-in-cell phenomena, where both cells remain alive (≥ 1 neoplastic cell) include entosis, emperipolesis, cannibalism, with the host cell not always being an immune cell. Examples of conspecific killing between non-neoplastic cells include phagocytosis, entosis, cannibalism, with the host cell not always being an immune cell. Examples of conspecific cell-in-cell phenomena between non-neoplastic cells, where both cells remain alive, include emperipolesis, with the host cell not always being an immune cell. Phagocytosis, heterotrophy, and bacterivory are examples of heterospecific killing. Phagocytosis and endosymbiosis are examples of heterospecific cell-in cell phenomena, where both cells remain alive. A green box indicates that the specific cell-in-cell category type has been found in that taxon, whereas an orange box indicates no heterospecific or conspecific cell-in-cell phenomena, i.e., researchers searched for heterospecific or conspecific cell-in-cell phenomena in these taxa but did not find such phenomena. NA shows that cell-in-cell phenomena have not been searched for in these taxa by researchers. Detailed information about the genes can be found in Supplementary Table 3. *No cancer-like phenomena reported.
