Ji-Seon Lee1, Jeong-Rak Park1, Ok-Seon Kwon1, Tae-Hee Lee1, Ichiro Nakano1, Hiroyuki Miyoshi1, Kwang-Hoon Chun1, Myung-Jin Park1, Hong Jun Lee1, Seung U Kim1, Hyuk-Jin Cha1. 1. Department of Life Sciences, Sogang University, Seoul, Korea (J.-S.L., J.-R.P., O.-S.K., H.-J.C.); Laboratory of Cancer and Stem Cell Biology, Sejong University, Seoul, Korea (T.-H.L.); Department of Neurological Surgery, The Ohio State University, Columbus, Ohio, (I.N.); Subteam for Manipulation of Cell Fate, RIKEN BioResource Center, Wako, Japan (H.M.); Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Korea (K.-H.C.); Divisions of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea (M.-J.P.); College of Medicine, Chung-Ang University, Seoul, Korea (H.J.L., S.U.K.); Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada (H.J.L., S.U.K.).
Abstract
BACKGROUND: Cancer stemness, observed in several types of glioma stem cells (GSCs), has been demonstrated to be an important barrier for efficient cancer therapy. We have previously reported that cancerous neural stem cells (F3.Ras.CNSCs), derived from immortalized human neural stem cells by a single oncogenic stimulation, form glial tumors in vivo. METHOD: We searched for a commonly expressed stress modulator in both F3.Ras.CNSCs and GSCs and identified silent mating type information regulation 2, homolog (SIRT1) as a key factor in maintaining cancer stemness. RESULT: We demonstrate that the expression of SIRT1, expressed in "cancer cells with neural stemness," is critical not only for the maintenance of stem cells, but also for oncogenic transformation. Interestingly, SIRT1 is essential for the survival and tumorigenicity of F3.Ras.CNSCs and GSCs but not for the U87 glioma cell line. CONCLUSION: These results indicate that expression of SIRT1 in cancer cells with neural stemness plays an important role in suppressing p53-dependent tumor surveillance, the abrogation of which may be responsible not only for inducing oncogenic transformation but also for retaining the neural cancer stemness of the cells, suggesting that SIRT1 may be a putative therapeutic target in GSCs.
BACKGROUND:Cancer stemness, observed in several types of glioma stem cells (GSCs), has been demonstrated to be an important barrier for efficient cancer therapy. We have previously reported that cancerous neural stem cells (F3.Ras.CNSCs), derived from immortalized human neural stem cells by a single oncogenic stimulation, form glial tumors in vivo. METHOD: We searched for a commonly expressed stress modulator in both F3.Ras.CNSCs and GSCs and identified silent mating type information regulation 2, homolog (SIRT1) as a key factor in maintaining cancer stemness. RESULT: We demonstrate that the expression of SIRT1, expressed in "cancer cells with neural stemness," is critical not only for the maintenance of stem cells, but also for oncogenic transformation. Interestingly, SIRT1 is essential for the survival and tumorigenicity of F3.Ras.CNSCs and GSCs but not for the U87 glioma cell line. CONCLUSION: These results indicate that expression of SIRT1 in cancer cells with neural stemness plays an important role in suppressing p53-dependent tumor surveillance, the abrogation of which may be responsible not only for inducing oncogenic transformation but also for retaining the neural cancer stemness of the cells, suggesting that SIRT1 may be a putative therapeutic target in GSCs.
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