The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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11. MYC determines lineage commitment in KRAS-driven primary liver cancer development
D’Artista, L. et al. Journal of Hepatology. 79(1):141-149 (2023).
doi: 10.1016/j.jhep.2023.02.039.
Summary, future impact and graphical abstract by Alexandra Boitor, EACR Scientific Officer
Summary of the findings
In this paper, D’Artista et al are investigating both the “cell of origin” and the molecular mechanisms that govern the development of primary tumours in the liver. Building upon previous work demonstrating that hepatocytes pose increased plasticity, the authors implicate MYC as a master regulator in lineage commitment in primary liver cancer. More exactly, the authors of this paper suggest that high MYC levels and MYC controlled transcriptional activity of FOXA1, FOXA2 and ETS1 can determine the commitment of malignant hepatocytes towards hepatocellular carcinoma. The overexpression of Ets1 together with shRNA targeting Foxa1 and Foxa2 in MYC transformed hepatocytes caused a switch from hepatocellular carcinoma to intrahepatic cholangiocarcinoma development (as shown in the Figure).
Future impact
The authors highlight the relevance of their findings for regenerative medicine and modulation of cancer response to treatment.
11. MYC determines lineage commitment in KRAS-driven primary liver cancer development