betaIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer
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.
|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.;|
|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|