| First Author | Huynh N | Year | 2017 |
| Journal | BMC Cancer | Volume | 17 |
| Issue | 1 | Pages | 431 |
| PubMed ID | 28629331 | Mgi Jnum | J:273566 |
| Mgi Id | MGI:6282758 | Doi | 10.1186/s12885-017-3432-0 |
| Citation | Huynh N, et al. (2017) Depletion of p21-activated kinase 1 up-regulates the immune system of APC(14/+) mice and inhibits intestinal tumorigenesis. BMC Cancer 17(1):431 |
| abstractText | 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. |
