βIII-Tubulin: A novel mediator of chemoresistance and metastases in pancreatic cancer
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Joshua A. McCarroll2,3,*, George Sharbeen1,*, Jie Liu1,*, Janet Youkhana1, David Goldstein1,4, Nigel McCarthy2, Lydia F. Limbri1, Dominic Dischl5, Güralp O. Ceyhan5, Mert Erkan6, Amber L. Johns7, Andrew V. Biankin7,8, Maria Kavallaris2,3 and Phoebe A. Phillips1
1 Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia
2 Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Australia, Sydney, Australia
3 ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, Australia
4 Prince of Wales Hospital, Prince of Wales Clinical School, Sydney, NSW, Australia
5 Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
6 Department of Surgery Koc University School of Medicine, Istanbul, Turkey
7 The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
8 Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom
* These authors contributed equally to this work
Phoebe A. Phillips, email:
Maria Kavallaris, email:
Keywords: Pancreatic cancer, chemoresistance, tumor growth, metastases, βIII-tubulin
Received: September 25, 2014 Accepted: December 09, 2014 Published: December 10, 2014
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.
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