@article{028e4ad00c2b4c3d8bb34c71aa6f8a7d,
title = "Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models",
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.",
author = "Nguyen, {Liem H.} and Robinton, {Daisy A.} and Seligson, {Marc T.} and Linwei Wu and Lin Li and Dinesh Rakheja and Comerford, {Sarah A.} and Saleh Ramezani and Xiankai Sun and Parikh, {Monisha S.} and Yang, {Erin H.} and Powers, {John T.} and Gen Shinoda and Shah, {Samar P.} and Hammer, {Robert E.} and Daley, {George Q.} and Hao Zhu",
note = "Funding Information: We thank S.J. Morrison for providing the Ubiquitin-Cre/ERT2 mice, Joshua Mendell for providing the LAP-tTA and TRE-MYC mice, and Roderick Bronson and the Harvard Medical School Rodent Histopathology Core and John Shelton and the UTSW Richardson Molecular Pathology Core for mouse tissue pathology and diagnostic interpretation. D.R. is supported by a Cancer Prevention and Research Institute of Texas grant (RP101195-C3) to study the genetics and biology of liver tumorigenesis in children. This work was supported by a grant from the Ellison Medical Foundation and the NIH (R01 GM107536) (to G.Q.D.). G.Q.D. is an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. This work was also supported by an American Cancer Society Postdoctoral Fellowship, by NIH K08 Grant1K08CA157727-02, by a Burroughs Welcome Career Medical Award, and by a Cancer Prevention and Research Institute of Texas New Investigator grant (to H.Z.). ",
year = "2014",
month = aug,
day = "11",
doi = "10.1016/j.ccr.2014.06.018",
language = "English (US)",
volume = "26",
pages = "248--261",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}
