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betaIII-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, beta-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of beta-tubulins in pancreatic cancer are unknown. We measured the expression of different beta-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence betaIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of betaIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that betaIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing betaIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of betaIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that betaIII-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.

Type Journal
ISBN 1949-2553 (Electronic) 1949-2553 (Linking)
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.; Phillips, P. A.;
Publisher Name Oncotarget
Published Date 2015-01-01
Published Volume 6
Published Issue 4
Published Pages 2235-2249
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/pubmed/25544769
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/12840