The mTOR pathway is a major signaling cascade regulating tumor cell growth and metabolism . Thus, targeting the mTOR pathway is considered to be a valid therapeutic approach for cancer treatment . Studies of mTOR pathway in HB are still scanty. Hartmann et al. reported that in 24 human HB specimens, p-mTOR expression was detected in 96% (23/24) cases . Similarly, in the present study, we show the activation of mTORC1 (as revealed by p-4EBP1 immunohistochemistry) in the large majority of HB specimens from an independent collection. In addition, it has been found that Rapamycin inhibits proliferation and induces apoptosis in HepG2, HepT1, and Huh6 human HB cells in vitro. Rapamycin also suppresses Huh6 growth in a xenograft model . Altogether, these data indicate that mTOR, and particularly mTORC1, is frequently activated in human HB. Thus, targeting mTORC1 might be beneficial for HB treatment. However, the mechanisms promoting mTORC1 activation in HB were not investigated to date. In our current investigation, we provide a novel mechanism by which YAP and TAZ activate mTORC1, namely via transcriptional upregulation of SLC38A1. In this regard, the concordant data obtained in the YAP/β-catenin mouse model, HB cell lines, and human HB specimens strongly suggest that the same mechanism of mTORC1 induction is at play along murine and human HB development. Nonetheless, larger human HB collections should be analyzed to further substantiate the present findings. Although we found that YAP contributes to HB development via activation of mTORC1, we cannot exclude that YAP promotes HB occurrence also through additional molecular mechanisms. For instance, it has been recently shown that the transcription factor Forkhead Box M1 (FOXM1) is a major player along hepatocellular carcinoma development driven by YAP overexpression . Preliminary data from our laboratory show that the functional interplay between YAP and FOXM1 is also present in human HB cell lines (Supplementary Figure 1). Additional investigation is required to determine the importance of FOXM1 in YAP-dependent HB development.