title: CD133 Modulate HIF-1α Expression under Hypoxia in EMT Phenotype Pancreatic Cancer Stem-Like Cells.
abstract: Although CD133 is a known representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia is not fully known. The aim of this study is to demonstrate that CD133 regulates hypoxia inducible factor (HIF)-1α expression with tumor migration. The CD133⁺ pancreatic cancer cell line, Capan1M9, was compared with the CD133(-) cell line, shCD133M9, under hypoxia. HIF-1α expression levels were compared by Western blot, HIF-1α nucleus translocation assay and real-time (RT)-PCR. The hypoxia responsive element (HRE) was observed by luciferase assay. The migration ability was analyzed by migration and wound healing assays. Epithelial mesenchymal transition (EMT) related genes were analyzed by real-time RT-PCR. HIF-1α was highly expressed in Capan1M9 compared to shCD133M9 under hypoxia because of the high activation of HRE. Furthermore, the migration ability of Capan1M9 was higher than that of shCD133M9 under hypoxia, suggesting higher expression of EMT related genes in Capan1M9 compared to shCD133M9.
  
  
  CONCLUSIONS
  HIF-1α expression under hypoxia in CD133⁺ pancreatic cancer cells correlated with tumor cell migration through EMT gene expression. Understanding the function of CD133 in cancer aggressiveness provides a novel therapeutic approach to eradicate pancreatic cancer stem cells.
authors.affiliation: Division of Cancer and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. maeda-k@m3.kufm.kagoshima-u.ac.jp.|Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. maeda-k@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Koki
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Division of Cancer and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. colleen@m3.kufm.kagoshima-u.ac.jp.|Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Tronto, ON M5T 3M7, Canada. colleen@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Hematology and Immunology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. myoshimi@m.kufm.kagoshima-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimitsu
authors.affiliation: Division of Cancer and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. tkuwa@m2.kufm.kagoshima-u.ac.jp.|Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. tkuwa@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Taisaku
authors.initials: T
authors.lastname: Kuwahata
authors.affiliation: Division of Cancer and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. yu-mi@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Division of Cancer and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. kt4494@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Koichirou
authors.initials: K
authors.lastname: Tsukasa
authors.affiliation: Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. t-hayasi@m.kufm.kagoshima-u.ac.jp.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. shinchi@m.kufm.kagoshima-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shinchi
authors.affiliation: Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. natsugoe@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.affiliation: Center for Innovative Therapy Research and Application, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. sonshin@m2.kufm.kagoshima-u.ac.jp.|Tanegashima Medical Center, 7463 Nishi-no-omote, Nishi-no-omote 891-3198, Japan. sonshin@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Sonshin
authors.initials: S
authors.lastname: Takao
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: CD133; EMT; HIF-1α; cancer stem cell; hypoxia; migration; pancreatic cancer