Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice
Name
Anderson_Nanoparticle-formulated.pdf
Size
4.33 MB
Format
Adobe PDF
Checksum (MD5)
e53c3522897067b1c742298cf424f854
Author(s)
Yin, Hao
Zeigerer, Anja
Nonaka, Hidenori
Zerial, Marino
Koteliansky, Victor
Anderson, Daniel Griffith
Ruda, Vera
Bogorad, Roman
Date Issued
May 2014
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Bogorad, Roman L., Hao Yin, Anja Zeigerer, Hidenori Nonaka, Vera M. Ruda, Marino Zerial, Daniel G. Anderson, and Victor Koteliansky. “Nanoparticle-Formulated siRNA Targeting Integrins Inhibits Hepatocellular Carcinoma Progression in Mice.” Nat Comms 5 (May 21, 2014).
Version
Author's final manuscript
Abstract
Integrins play an important role during development, regulating cell differentiation, proliferation and survival. Here we show that knockdown of integrin subunits slows down the progression of hepatocellular carcinoma (HCC). Using nanoparticulate delivery of short interfering RNAs targeting β1 and αv integrin subunits, we downregulate all integrin receptors in hepatocytes. Short-term integrin knockdown (2 weeks) does not cause apparent structural or functional perturbations of normal liver tissue. Alterations in liver morphology accumulate on sustained integrin downregulation (7 weeks). The integrin knockdown leads to significant retardation of HCC progression, reducing proliferation and increasing tumour cell death. This tumour retardation is accompanied by reduced activation of the MET oncogene as well as expression of its mature form on the cell surface. Our data suggest that transformed proliferating cells from HCC are more sensitive to knockdown of integrins than normal quiescent hepatocytes, highlighting the potential of small interfering RNA-mediated inhibition of integrins as an anti-cancer therapeutic approach.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/ncomms4869
