title: βIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer.
abstract: Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, β-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of β-tubulins in pancreatic cancer are unknown. We measured the expression of different β-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence βIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of βIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that βIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing βIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of βIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that βIII-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients.
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Australia, Sydney, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, Australia.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: McCarroll
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Sharbeen
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia.
authors.forename: Janet
authors.initials: J
authors.lastname: Youkhana
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia.|Prince of Wales Hospital, Prince of Wales Clinical School, Sydney, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Australia, Sydney, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: McCarthy
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia.
authors.forename: Lydia F
authors.initials: LF
authors.lastname: Limbri
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Dischl
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Güralp O
authors.initials: GO
authors.lastname: Ceyhan
authors.affiliation: Department of Surgery Koc University School of Medicine, Istanbul, Turkey.
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.affiliation: The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Johns
authors.affiliation: The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.|Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Australia, Sydney, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Kavallaris
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia.
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Phillips
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D000067492:RNAi Therapeutics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C498585:TUBB3 protein, human; D014404:Tubulin