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Article Addendum
Roles of mTOR and STAT3 in Autophagy Induced by Telomere 3' Overhang-Specific DNA Oligonucleotides
Tomohisa Yokoyama, Yasuko Kondo and Seiji Kondo
volume 3 | issue 5
September/October 2007Pages: 496 - 498
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Telomere 3' overhang-specific DNA oligonucleotides (T-oligos) induce cancer cell death, presumably by mimicking telomere loop disruption and are, therefore, considered a promising new therapeutic strategy. We previously demonstrated that T-oligos inhibit the proliferation of malignant glioma cells in vitro and in vivo by inducing non-apoptotic autophagy. Using a reverse-phase protein microarray analysis and Western blotting, we revealed that T-oligos inhibit the mammalian target of rapamycin (mTOR) and the signal transducer and activator of transcription 3 (STAT3). Moreover, rapamycin (mTOR inhibitor) and AG490 (STAT3 inhibitor) sensitize malignant glioma cells to T-oligos by augmenting autophagy. Although mTOR is well known as a negative regulator of autophagy, the relationship between STAT3 and autophagy has never been demonstrated, to our knowledge. These findings suggest that, by exhibiting a novel mechanism of inducing autophagy through inhibition of mTOR and STAT3, T-oligos are a promising therapeutic agent for treating malignant gliomas. Here, we discuss evidence for T-oligos’ effects on cell signaling pathways that may explain their ability to stimulate autophagy by inhibiting STAT3 as well as mTOR.
Addendum to:
Telomere 3' Overhang-Specific DNA Oligonucleotides Induce Autophagy in Malignant Glioma Cells
H. Aoki, E. Iwado, M.S. Eller, Y. Kondo, K. Fujiwara, G.-Z. Li, K.R. Hess, D.R. Siwak, R. Sawaya, G.B. Mills, B.A. Gilchrest and S. Kondo
FASEB J 2007; Epub ahead of print
Authors
Tomohisa Yokoyama
University of Texas MD Anderson Cancer Center
Yasuko Kondo
University of Texas MD Anderson Cancer Center
Seiji Kondo
University of Texas MD Anderson Cancer Center
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.