βIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer

McCarroll, J. A. et al. (2015) βIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer. Oncotarget, 6(4), pp. 2235-2249. (PMID:25544769) (PMCID:PMC4385848)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Biankin, Professor Andrew
• Authors: McCarroll, J. A., Sharbeen, G., Liu, J., Youkhana, J., Goldstein, D., McCarthy, N., Limbri, L. F., Dischl, D., Ceyhan, G. O., Erkan, M., Johns, A. L., Biankin, A. V., Kavallaris, M., and Phillips, P. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncotarget
• Publisher: Impact Journals
• ISSN: 1949-2553
• ISSN (Online): 1949-2553
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in OncoTarget 6(4):2235-2249
• Publisher Policy: Reproduced under a Creative Commons License