DUX4 expression in cancer induces a metastable early embryonic totipotent program

The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells. DUX4 expression activates the DUX4-regulated ZGA transcriptional program, the subsequent 8C-like program, and markers of early embryonic lineages, while suppressing steady-state and interferon-induced MHC class I expression. Although DUX4 was expressed in a small number of cells under standard culture conditions, DNA damage or changes in growth conditions increased the fraction of cells expressing DUX4 and its downstream programs. Our demonstration that transient expression of endogenous DUX4 in cancer cells induces a metastable early embryonic stem cell program and sup-presses antigen presentation has implications for cancer growth, progression, and immune evasion.

Automated summary

The transcription factor DUX4 plays a role in regulating the early embryonic stem cell program in cancer cells. It is expressed transiently in a small subset of cells, activating the gene expression program associated with early embryonic lineages while suppressing certain proteins. Changes in growth conditions or DNA damage can increase the expression of DUX4.