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. 2021 Jun 2;9:682619. doi: 10.3389/fcell.2021.682619

FIGURE 1.

FIGURE 1

Phylogenetic tree depicting the evolutionary relationships of metazoa and the emergence of metastasis in the cyclostome-to-chondrichthyes transition. Each phylogenetic group has manifested, for the first time, a key innovation that was conserved throughout the lineage. Red-colored clades indicate groups with lethal cancer types. Based on information derived from histological analyses, tumors were classified into benign (corresponding to initiation), malignant/non-metastatic (corresponding to promotion) or malignant, metastatic (corresponding to progression). Invasive and metastatic tumors have been reported from Chondrichthyes to mammals. The mollusks present contagious invasive cancer, while the urochordates are cancer-resistant. The red dot on the tree represents the common chordate ancestor, which gave rise to both, metastatic (green dots) and non-metastatic species (yellow dots). Model of the progression from a normal cell to metastatic cancer was modified from a previous illustration (Iacobuzio-Donahue et al., 2012). The origins of a closed circulatory system and of acquired immunity are also presented.