title: Krüpple-like factor 10 regulates radio-sensitivity of pancreatic cancer via UV radiation resistance-associated gene.
abstract: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown.
  
  
  
  Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay. Orthotopic murine tumor model and clinical specimens were used to evaluate radio-sensitivity of pancreatic cancer.
  
  
  
  We found Klf10 silencing correlates with enhanced pancreatic cancer clonogenic survival and murine tumor growth after radiation. UVRAG was an essential down-stream mediator transcriptionally suppressed by Klf10. Silencing UVRAG mRNA in Klf10 depleted Panc-1 cells reversed the radio-resistant phenotypes including decreased apoptosis and enhanced DNA repair as well as autophagy. Metformin, an anti-diabetic agent, was found to increase Klf10 and suppress UVRAG expression to improve radiation cytotoxicity in pancreatic cancer. The predictive value of Klf10 in radiation response and the inverse correlation with UVRAG were confirmed in cohorts of pancreatic cancer patients.
  
  
  
  Klf10 is a potential biomarker in predicting and sensitizing radiation effect in pancreatic cancer.
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Vincent Hung-Shu
authors.initials: VH
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County , Taiwan.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County , Taiwan.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Tsai
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Peng
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County , Taiwan.
authors.forename: Su-Liang
authors.initials: SL
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County , Taiwan.
authors.forename: Tsung Ming
authors.initials: TM
authors.lastname: Chang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Winston Chun-Yuan
authors.initials: WC
authors.lastname: Yu
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli County , Taiwan; Department of Radiation Oncology, Taipei Municipal Wanfang Hospital, Taiwan. Electronic address: hjmc@nhri.org.tw.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Ch'ang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D045744:Cell Line, Tumor; D004260:DNA Repair; D051765:Early Growth Response Transcription Factors / Q000032:analysis / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000032:analysis / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D016212:Transforming Growth Factor beta; D008687:Metformin; D055372:AMP-Activated Protein Kinases
keywords: Krüpple-like factor 10; Pancreatic cancer; Radio-sensitivity; UV radiation resistance-associated gene