Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
Name
Goldberg-2012-Pyruvate kinase M2-s.pdf
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2.4 MB
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Adobe PDF
Checksum (MD5)
7a6b6bb35463bf0b5caee20cc8416e56
Author(s)
Goldberg, Michael Solomon
Sharp, Phillip A.
Date Issued
January 2012
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press, The
Citation
Goldberg, M. S., and P. A. Sharp. “Pyruvate Kinase M2-specific siRNA Induces Apoptosis and Tumor Regression.” Journal of Experimental Medicine 209.2 (2012): 217–224. Web. 3 May 2012.
Version
Final published version
Abstract
The development of cancer-specific therapeutics has been limited because most healthy cells and cancer cells depend on common pathways. Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms. PKM2, whose expression in cancer cells results in aerobic glycolysis and is suggested to bestow a selective growth advantage, is a promising target. Because many oncogenes impart a common alteration in cell metabolism, inhibition of the M2 isoform might be of broad applicability. We show that several small interfering (si) RNAs designed to target mismatches between the M2 and M1 isoforms confer specific knockdown of the former, resulting in decreased viability and increased apoptosis in multiple cancer cell lines but less so in normal fibroblasts or endothelial cells. In vivo delivery of siPKM2 additionally causes substantial tumor regression of established xenografts. Our results suggest that the inherent nucleotide-level specificity of siRNA can be harnessed to develop therapeutics that target isoform-specific exons in genes exhibiting differential splicing patterns in various cell types.
Description
Online supplemental material is available at http://www.jem.org/cgi/content/full/jem.20111487/DC1.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported
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DOI of Published Version
https://doi.org/10.1084/jem.20111487
