Abstract 5977: Maf1 suppresses hepatocarcinogenesis in mice through inhibition of Akt-mTOR signaling

Abstract

Abstract Maf1 is a transcriptional repressor downstream of mTORC1by inhibiting transcription of lipogenic genes by RNA Pol II and ribosomal/transfer RNA genes by RNA Pol III. We recently showed that Maf1 suppresses the growth of cultured liver cancer cells and xenograft tumors by blocking Akt-mTOR signaling through the tumor suppressor PTEN. However, whether Maf1 has tumor suppressor activity has never been demonstrated in physiologically relevant tumor models. Here, we investigated the role of Maf1 in hepatocarcinogenesis in NRas/Akt- and c-Myc-driven mouse liver cancer models generated by hydrodynamic transfection (HDT). We found that Maf1 or Maf1-4A, a non-phosphorylatable and active form of Maf1, significantly attenuated the development of NRas/Akt-driven liver tumors. On the other hand, while knockdown of Maf1 alone did not cause any discernible abnormality in the mouse liver, down-regulation of Maf1 markedly accelerated c-Myc-induced liver tumor development. At the molecular level, Maf1 strongly suppressed phosphorylation of Akt-mTOR pathway components, including Akt and S6. Conclusions: Maf1 suppresses hepatocarcinogenesis through restraining Akt/mTOR signaling. These new findings provide first in vivo evidence that Maf1 is a liver tumor suppressor. Citation Format: Di Cao, Xiaoxing Li, Yang Yang, Yu-Feng Zhou, Mei-Yin Zhang, Shan-Shan Zhang, Qian-Nan Ren, Hui-Zhong Zhang, Yao-Jun Zhang, Shi-Juan Mai, Hui-Yun Wang. Maf1 suppresses hepatocarcinogenesis in mice through inhibition of Akt-mTOR signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5977.