Depletion of p21-activated kinase 1 up-regulates the immune system of APC∆14/+ mice and inhibits intestinal tumorigenesis
| Autor: | Mildred Yim, Mehrdad Nikfarjam, Chelsea Dumesny, Nhi Huynh, Graham S. Baldwin, Hong S. He, Mauro S. Sandrin, Kai Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Spleen Intestinal tumour Biology Stem cell marker lcsh:RC254-282 Flow cytometry 03 medical and health sciences 0302 clinical medicine Immune system PAK1 Genetics medicine Lymphocytes medicine.diagnostic_test Kinase lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens APC 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Immunology Cancer research Immunohistochemistry |
| Zdroj: | BMC Cancer, Vol 17, Iss 1, Pp 1-9 (2017) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-017-3432-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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