Title |
Depletion of p21-activated kinase 1 up-regulates the immune system of APC∆14/+ mice and inhibits intestinal tumorigenesis
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Published in |
BMC Cancer, June 2017
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DOI | 10.1186/s12885-017-3432-0 |
Pubmed ID | |
Authors |
Nhi Huynh, Kai Wang, Mildred Yim, Chelsea J. Dumesny, Mauro S. Sandrin, Graham S. Baldwin, Mehrdad Nikfarjam, Hong He |
Abstract |
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. 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. 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. 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 3 | 13% |
Student > Ph. D. Student | 2 | 9% |
Researcher | 2 | 9% |
Student > Master | 2 | 9% |
Student > Postgraduate | 2 | 9% |
Other | 3 | 13% |
Unknown | 9 | 39% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 3 | 13% |
Agricultural and Biological Sciences | 2 | 9% |
Neuroscience | 2 | 9% |
Medicine and Dentistry | 2 | 9% |
Other | 1 | 4% |
Unknown | 10 | 43% |