title: Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation.
abstract: OBJECTIVE
  Autophagy is frequently activated in radioresistant cancer cells. In the present study, we evaluated the role of autophagy and transforming growth factor-activated kinase 1 (TAK1) in radioresistance.
  
  
  METHODS
  TAK1 phosphorylation in MDA-MB231 breast cancer cells was evaluated by western blotting. The regulatory effects of the TAK1 inhibitor and autophagy inhibitor were assessed by cell morphology, cell survival and induction of apoptosis.
  
  
  RESULTS
  Radiation induced the phosphorylation of TAK1, whereas the inhibition of TAK1 activity enhanced the cytotoxicity of radiation in MDA-MB231 cells. Autophagy inhibitors significantly enhanced radiation-induced apoptosis of MDA-MB231 cells. This augmentation in radiosensitivity seemed to result from the suppression of TAK1 activation.
  
  
  CONCLUSIONS
  Inhibition of autophagy enhanced radiosensitivity through suppression of radiation-induced TAK1 activation, suggesting that the modulation of TAK1-induced autophagy may be a good therapeutic strategy to treat radioresistant breast cancer.
authors.affiliation: Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olymhic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea. sykim2@amc.seoul.kr and Seong Who Kim, MD, Ph.D., Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine Seoul, Republic of Korea. E-mail: swhokim@amc.seoul.kr.
authors.forename: Myung Woul
authors.initials: MW
authors.lastname: Han
authors.forename: Jong Cheol
authors.initials: JC
authors.lastname: Lee
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Gui Chul
authors.initials: GC
authors.lastname: Kim
authors.forename: Hyo Won
authors.initials: HW
authors.lastname: Chang
authors.forename: Hae Yun
authors.initials: HY
authors.lastname: Nam
authors.forename: Seong Who
authors.initials: SW
authors.lastname: Kim
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002738:Chloroquine / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011836:Radiation Tolerance / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000935:Antifungal Agents; D000962:Antimalarials; D002738:Chloroquine; D020930:MAP Kinase Kinase Kinases; D018942:Macrolides; D000099151:MAP Kinase Kinase Kinase 7; C040929:bafilomycin A1
keywords: Autophagy; TAK1; breast cancer; radioresistance