title: Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties.
abstract: Heat shock factor 1 (HSF1), a transcription factor activated by various stressors, regulates proliferation and apoptosis by inducing expression of target genes, such as heat shock proteins and Bcl-2 (B-cell lymphoma 2) interacting cell death suppressor (BIS). HSF1 also directly interacts with BIS, although it is still unclear whether this interaction is critical in the regulation of glioblastoma stem cells (GSCs). In this study, we examined whether small interfering RNA-mediated BIS knockdown decreased protein levels of HSF1 and subsequent nuclear localization under GSC-like sphere (SP)-forming conditions. Consistent with BIS depletion, HSF1 knockdown also reduced sex determining region Y (SRY)-box 2 (SOX2) expression, a marker of stemness, accompanying the decrease in SP-forming ability and matrix metalloprotease 2 (MMP2) activity. When HSF1 or BIS knockdown was combined with temozolomide (TMZ) treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose) polymerase (PARP) cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased. Taken together, our findings suggest that targeting BIS or HSF1 could be a viable therapeutic strategy for GSCs resistant to conventional TMZ treatment.
authors.affiliation: Department of Biochemistry, The Catholic University of Korea, Seoul 06591, Korea. milybud@gmail.com.|Institute for Aging and Metabolic Diseases, The Catholic University of Korea, Seoul 06591, Korea. milybud@gmail.com.|Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. milybud@gmail.com.
authors.forename: Chang-Nim
authors.initials: CN
authors.lastname: Im
authors.affiliation: Department of Biochemistry, The Catholic University of Korea, Seoul 06591, Korea. nice1205@hanmail.net.|Institute for Aging and Metabolic Diseases, The Catholic University of Korea, Seoul 06591, Korea. nice1205@hanmail.net.
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, The Catholic University of Korea, Seoul 06591, Korea. leejh@catholic.ac.kr.|Institute for Aging and Metabolic Diseases, The Catholic University of Korea, Seoul 06591, Korea. leejh@catholic.ac.kr.|Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. leejh@catholic.ac.kr.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D000077204:Temozolomide; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018906:Antineoplastic Agents, Alkylating; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D003606:Dacarbazine; D020778:Matrix Metalloproteinase 2; D000077204:Temozolomide
keywords: BIS; HSF1; apoptosis; glioblastoma; temozolomide