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Cancer Cell. 2014 Aug 11;26(2):248-61. doi: 10.1016/j.ccr.2014.06.018.

Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models.

Author information

1
Children's Research Institute, Departments of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
3
Children's Research Institute, Departments of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Organ Transplant Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
4
Departments of Pathology and Pediatrics, Children's Medical Center and University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
5
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
6
Department of Radiology and Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
7
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
8
Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: george.daley@childrens.harvard.edu.
9
Children's Research Institute, Departments of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: hao.zhu@utsouthwestern.edu.

Abstract

Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance.

PMID:
25117712
PMCID:
PMC4145706
DOI:
10.1016/j.ccr.2014.06.018
[Indexed for MEDLINE]
Free PMC Article

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