title: Anoxia/reoxygenation induces epithelial-mesenchymal transition in human colon cancer cell lines.
abstract: Epithelial-mesenchymal transition (EMT) is considered to be a crucial event in the development of cancer metastasis. Anoxia/reoxygenation (A/R) is known to occur in cancer tissues due to angiogenesis and changes in tissue pressure that occur during tumor growth. We investigated whether A/R induces EMT in the human colon cancer cell line HT-29. Colon cancer cells were exposed to anoxia (2 h) followed by reoxygenation (4-22 h) and evaluated for EMT changes using immunofluorescence and western blot analyses. We also investigated the expression of EMT-related transcription factors (Snail and ZEB1) using RT-PCR and evaluated the expression of NF-κB using ELISA. To determine whether NF-κB is involved in A/R-induced EMT, HT-29 cells were treated with proteasome inhibitors. Colon cancer cells exposed to A/R underwent EMT morphological changes; the cancer cells acquired a spindle-shaped phenotype. The expression of E-cadherin on the cell surface and the total amount of E-cadherin proteins were reduced after A/R. The expression of EMT-related transcription factors (Snail, ZEB1) was increased after A/R. Pretreatment with proteasome inhibitors significantly attenuated the downregulation of E-cadherin induced by A/R. These results indicate that A/R induces EMT in human colon cancer cells through an NF-κB-dependent transcriptional pathway.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Okajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Reiko
authors.initials: R
authors.lastname: Tsuchiya
authors.forename: Tatsuzo
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Satoko
authors.initials: S
authors.lastname: Adachi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okayama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kamada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D048430:Cell Shape; D003110:Colonic Neoplasms; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010100:Oxygen / Q000502:physiology*; D011485:Protein Binding; D000071250:Snail Family Transcription Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D052002:NF-kappa B p50 Subunit; C498143:RELA protein, human; D000071250:Snail Family Transcription Factors; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D010100:Oxygen