We first employed a systemic Igfbp3 knockout (KO) mouse model on an FVB/N background [35], wherein tongue tumors were established by exposure to 4-NQO, a water-soluble carcinogen that mainly generates tumors in the oral cavity [36,37], diluted in the drinking water, as previously described [27] (Figure 2A). This evidence concerns the gene IGFBP3 and tongue neoplasm.