학술논문
Ionizing Radiation Induces Resistant Glioblastoma Stem-Like Cells by Promoting Autophagy via the Wnt/β-Catenin Pathway.
Document Type
Academic Journal
Author
Tsai CY; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung 807, Taiwan.; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Ko HJ; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Huang CF; Department of Biotechnology and Laboratory Science in Medicine, Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.; Lin CY; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Chiou SJ; Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Su YF; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Lieu AS; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Loh JK; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Kwan AL; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung 807, Taiwan.; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Chuang TH; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung 807, Taiwan.; Immunology Research Center, National Health Research Institutes, Miaoli 350, Taiwan.; Hong YR; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung 807, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101580444 Publication Model: Electronic Cited Medium: Print ISSN: 2075-1729 (Print) Linking ISSN: 20751729 NLM ISO Abbreviation: Life (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2075-1729
Abstract
Therapeutic resistance in recurrent glioblastoma multiforme (GBM) after concurrent chemoradiotherapy (CCRT) is a challenging issue. Although standard fractionated radiation is essential to treat GBM, it has led to local recurrence along with therapy-resistant cells in the ionizing radiation (IR) field. Lines of evidence showed cancer stem cells (CSCs) play a vital role in therapy resistance in many cancer types, including GBM. However, the molecular mechanism is poorly understood. Here, we proposed that autophagy could be involved in GSC induction for radioresistance. In a clinical setting, patients who received radiation/chemotherapy had higher LC3II expression and showed poor overall survival compared with those with low LC3 II. In a cell model, U87MG and GBM8401 expressed high level of stemness markers CD133, CD44, Nestin, and autophagy marker P62/LC3II after receiving standard fractionated IR. Furthermore, Wnt/β-catenin proved to be a potential pathway and related to P62 by using proteasome inhibitor (MG132). Moreover, pharmacological inhibition of autophagy with BAF and CQ inhibit GSC cell growth by impairing autophagy flux as demonstrated by decrease Nestin, CD133, and SOX-2 levels. In conclusion, we demonstrated that fractionated IR could induce GSCs with the stemness phenotype by P62-mediated autophagy through the Wnt/β-catenin for radioresistance. This study offers a new therapeutic strategy for targeting GBM in the future.