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)

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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 > Institute 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

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