title: Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy.
abstract: BACKGROUND
  Recent studies demonstrated the importance of ADAM9 in prostate cancer relapse upon therapy. In this study, we determined the role of ADAM9 in the therapeutic resistance to radiation and chemotherapy.
  
  
  METHODS
  ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer cells. The sensitivity of ADAM9 knockdown cells toward radiation and chemotherapeutic agents were determined. Additionally, the effects of ADAM9 knockdown on prostate cancer cell morphology, biochemical and functional alterations were accessed.
  
  
  RESULTS
  Both transient and stable knockdown of ADAM9 resulted in increased apoptosis and increased sensitivity to radiation. ADAM9 knockdown also increased prostate cancer sensitivity to several chemotherapeutic drugs. ADAM9 knockdown resulted in increased E-cadherin and altered integrin expression and underwent phenotypic epithelial transition. These were reflected by the morphological, biochemical, and functional alterations in the ADAM9 knockdown cells.
  
  
  CONCLUSIONS
  ADAM9 plays a crucial role in prostate cancer progression and therapeutic resistance in part by altering E-cadherin and integrin expression. ADAM9 is an important target for the consideration of treating prostate cancer patients who developed therapeutic resistance and disease relapse.
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. sajni.josson@cshs.org
authors.forename: Sajni
authors.initials: S
authors.lastname: Josson
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Anderson
authors.forename: Shian-Ying
authors.initials: SY
authors.lastname: Sung
authors.forename: Peter A S
authors.initials: PA
authors.lastname: Johnstone
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kubo
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Hsieh
authors.forename: Rebecca
authors.initials: R
authors.lastname: Arnold
authors.forename: Murali
authors.initials: M
authors.lastname: Gururajan
authors.forename: Clayton
authors.initials: C
authors.lastname: Yates
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
mesh_terms: D051722:ADAM Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015820:Cadherins / Q000032:analysis; D045744:Cell Line, Tumor; D004848:Epithelium / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011836:Radiation Tolerance; D013481:Superoxides / Q000032:analysis
chemical_list: D015820:Cadherins; D016023:Integrins; D008565:Membrane Proteins; D013481:Superoxides; D051722:ADAM Proteins; C098339:ADAM9 protein, human