title: Slug contributes to gemcitabine resistance through epithelial-mesenchymal transition in CD133(+) pancreatic cancer cells.
abstract: CD133-positive pancreatic cancer is correlated with unfavorable survival despite current development of therapy. Slug acts as a master regulator of epithelial-mesenchymal transition (EMT) which is the essential process in cancer progression. The aim of this study was to investigate the role of Slug in gemcitabine treatment for CD133-positive pancreatic cancer cells. We used a previously established pancreatic cancer cell line expressing high level of CD133 (Capan-1M9), which also expresses high level of Slug. We generated Slug knock-down subclone (shSlug M9) from this cell line, and compared expression of EMT-related genes, migration, invasion and gemcitabine resistance between two cell lines. Slug knock-down in CD133-positive pancreatic cancer cell line led to the reduction of migration and invasion ability. Furthermore, Slug knock-down sensitized CD133-positive pancreatic cancer cell line to gemcitabine. These results suggest that Slug plays an important role in not only invasion ability through EMT but also gemcitabine resistance of CD133-positive pancreatic cancer cells.
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsukasa
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.|Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Tronto, Canada.
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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimitsu
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Shyuichiro
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. sonshin@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Sonshin
authors.initials: S
authors.lastname: Takao
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D000093542:Gemcitabine
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: CD133; Chemoresistance; Gemcitabine; Pancreatic cancer; Slug