Depletion of p21-activated kinase 1 up-regulates the immune system of APC(Delta 14/+) mice and inhibits intestinal tumorigenesis
Web of Science
AuthorHuynh, N; Wang, K; Yim, M; Dumesny, CJ; Sandrin, MS; Baldwin, GS; Nikfarjam, M; He, H
Source TitleBMC Cancer
PublisherBIOMED CENTRAL LTD
University of Melbourne Author/sHuynh, Nhi; Sandrin, Mauro; Baldwin, Graham; Nikfarjam, Mehrdad; He, Hong; Wang, Kai; Yim, Mildred; Dumesny, Chelsea
AffiliationSurgery (Austin & Northern Health)
Medicine and Radiology
Document TypeJournal Article
CitationsHuynh, N., Wang, K., Yim, M., Dumesny, C. J., Sandrin, M. S., Baldwin, G. S., Nikfarjam, M. & He, H. (2017). Depletion of p21-activated kinase 1 up-regulates the immune system of APC(Delta 14/+) mice and inhibits intestinal tumorigenesis. BMC CANCER, 17 (1), https://doi.org/10.1186/s12885-017-3432-0.
Access StatusOpen Access
BACKGROUND: P21-activated kinase 1 (PAK1) stimulates growth and metastasis of colorectal cancer (CRC) through activation of multiple signalling pathways. Up-regulation of CRC stem cell markers by PAK1 also contributes to the resistance of CRC to 5-fluorouracil. The aim of this study was to investigate the effect of PAK1 depletion and inhibition on the immune system and on intestinal tumour formation in APC∆14/+ mice. METHODS: The PAK1 KO APC∆14/+ mice were generated by cross-breeding of PAK1 KO mice with APC∆14/+ mice. Splenic lymphocytes were analysed by flow cytometry, and immunohistochemical staining. The numbers of intestinal tumours were counted. Blood cells were also counted. RESULTS: Compared to APC+/+ mice, the numbers of both T- and B- lymphocytes were reduced in the spleen of APC∆14/+ mice. Depletion of PAK1 in APC∆14/+ mice increased the numbers of splenic T- and B- lymphocytes and decreased the numbers of intestinal tumours. Treatment of APC∆14/+ mice with PF-3758309, a PAK inhibitor reduced the numbers of intestinal tumours and increased the numbers of blood lymphocytes. CONCLUSION: Depletion of active PAK1 up-regulates the immune system of APC∆14/+ mice and suppresses intestinal tumour development. These observations suggest an important role for PAK1 in the immune response to tumours.
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