Embryonic Origins of Cancer: Insights from Double Homeobox 4 Regulation

Embryogenesis and tumorigenesis share several key biological characteristics, such as rapid cell proliferation, high plasticity, and immune evasion. This similarity indicates that developmental pathways can be hijacked, leading to the formation of malignant cell states. With regard to this, cancer can be regarded as a stem cell disease. On the contrary, a fetus, in many ways, has similar characteristics to the "ideal tumor", such as immune evasion and rapid growth. Therefore, deciphering the molecular mechanisms beneath these phenomena will help us to understand the embryonic origins of cancer. This review discusses the relationship between embryogenesis and tumorigenesis, highlighting the potential roles played by DUX4. DUX4 is involved in the activation of the zygote genome and then facilitates the establishment of totipotency in pre-implantation embryos, whereas the misexpression of DUX4 is associated with different types of cancer. Taken together, this indicates that DUX4 performs analogous functions in these two processes and connects embryogenesis and tumorigenesis. Through examining DUX4, this review underscores the importance of developmental mechanisms in cancer biology, suggesting that the insights gained from studying embryonic processes may provide novel therapeutic strategies. As we continue to explore the complex relationship between cancer and embryogenesis, elucidating the role of DUX4 in linking these two processes will be critical for developing targeted therapies that exploit developmental pathways.