Author
Listed:
- Roman L. Bogorad
(David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)
- Hao Yin
(David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)
- Anja Zeigerer
(Max Planck Institute of Molecular Cell Biology and Genetics)
- Hidenori Nonaka
(Max Planck Institute of Molecular Cell Biology and Genetics)
- Vera M. Ruda
(David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)
- Marino Zerial
(Max Planck Institute of Molecular Cell Biology and Genetics)
- Daniel G. Anderson
(David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Massachusetts Institute of Technology
Harvard-MIT Division of Health Sciences and Technology
Institute of Medical Engineering and Science, Massachusetts Institute of Technology)
- Victor Koteliansky
(David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Skolkovo Institute of Science and Technology, ul. Novaya, d.100, Skolkovo 143025, Russian Federation)
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.
Suggested Citation
Roman L. Bogorad & Hao Yin & Anja Zeigerer & Hidenori Nonaka & Vera M. Ruda & Marino Zerial & Daniel G. Anderson & Victor Koteliansky, 2014.
"Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice,"
Nature Communications, Nature, vol. 5(1), pages 1-14, September.
Handle:
RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4869
DOI: 10.1038/ncomms4869
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