Roles of mTOR and STAT3 in Autophagy Induced by Telomere 3' Overhang-Specific DNA Oligonucleotides
Year: 2007
Type: article
Abstract: 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 CellsH. 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. KondoFASEB J 2007; Epub ahead of print
Source: Autophagy
DOI: 10.4161/auto.4602
Authors: Tomohisa Yokoyama, Yasuko Kondo, Seiji Kondo
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2011808930