Global and specific mechanisms stimulate mistranslation in cancer.

ADAR1 and FTSJ1 enzymes promote tryptophan-to-phenylalanine mistranslation in cancer cells, with levels elevated across many cancer types.

• Why it matters: Understanding how cancer cells adapt to anti-tumor immune responses by altering protein synthesis can reveal new therapeutic targets and mechanisms of immune evasion.
• What they did: Researchers screened for genes regulating W→F substitutants under interferon-γ-induced tryptophan shortage, identifying ADAR1 and FTSJ1 as key regulators through molecular and genetic analyses.
• The result: Findings show ADAR1 supports ribosome quality control essential for mistranslation, while FTSJ1 methylates tRNA Trp to specifically drive W→F substitution, enabling cancer cells to respond adaptively to immune attack.