Depletion of p21-activated kinase 1 up-regulates the immune system of APC∆14/+ mice and inhibits intestinal tumorigenesis
N Huynh, K Wang, M Yim, CJ Dumesny, MS Sandrin… - BMC cancer, 2017 - Springer
N Huynh, K Wang, M Yim, CJ Dumesny, MS Sandrin, GS Baldwin, M Nikfarjam, H He
BMC cancer, 2017•SpringerAbstract 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/+ …
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/+ …
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.
Springer
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