Journal article
Plastic hepatocyte states limit liver cancer development
Nature communications, v 16(1), 11647
26 Nov 2025
PMID: 41290681
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The liver has remarkable regenerative capacity owing to the boundless proliferative potential of hepatocytes. During liver injury, sustained regeneration must be balanced by mechanisms limiting overgrowth and tumorigenesis. Epithelial plasticity is frequently observed during liver damage and is thought to mediate production of biliary epithelial cells (BECs) or hepatocytes, depending on tissue needs. Here we show that hepatocytes persisting in plastic states are present in virtually all liver injury contexts, representing the predominant outcome of hepatocyte reprogramming rather than their full BEC conversion. By developing tools to trap mouse hepatocytes in plastic states in vivo and using models of regeneration and transplantation, we show that plastic hepatocytes are refractory to proliferation cues from the microenvironment. Unlike terminally differentiated hepatocytes, plastic hepatocytes resist proliferation driven by endogenous oncogenic stimuli. Thus, acquisition of plastic states represents a protective mechanism that constrains hepatocyte proliferation, limiting overgrowth and tumorigenesis during liver disease.
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Details
- Title
- Plastic hepatocyte states limit liver cancer development
- Creators
- Lauren S. Strathearn - Fox Chase Cancer CenterYuki Hayata - Fox Chase Cancer CenterAbhinav Illendula - Fox Chase Cancer CenterCharles K. Hewett - Fox Chase Cancer CenterMingjia Chen - Fox Chase Cancer CenterGuoshun He - Fox Chase Canc Ctr, Canc Signaling & Microenvironm Program, Philadelphia, PA 19111 USAMaria Escribano-Cebrian - Fox Chase Cancer CenterBrianna Jarboe - Drexel UniversityLaura Gomez-Tome - Fox Chase Cancer CenterNicola de Prisco - Fox Chase Cancer CenterMichael Slifker - Fox Chase Cancer CenterSatoshi Kawamura - Mie UniversityHayato Nakagawa - Mie UniversityDavid Rossell - Universitat Pompeu FabraBen Z. Stanger - University of PennsylvaniaJoan Font-Burgada - Fox Chase Cancer Center
- Publication Details
- Nature communications, v 16(1), 11647
- Publisher
- Nature Publishing
- Number of pages
- 15
- Grant note
- DP2CA258224 / U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) T32GM142606 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P30CA006927; R01CA289703 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:001651009300003
- Scopus ID
- 2-s2.0-105026319534
- Other Identifier
- 991022197393604721
UN Sustainable Development Goals (SDGs)
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology