 Thyroid hormones have an important role in fostering tumor progression, however their upstream regulators are less clear. Here, the authors identify the thyroid hormone-activating enzyme type 2 diodinase as a P53 target gene and demonstrate its contribution to tumor progression in P53 mutant squamous cell carcinoma. This article was authored by Anna Rita Knappi, Katerina Murrow, Antonio Pozzoni, and others.