摘要
Protein tyrosine phosphatase non-receptor type 18(PTPN18)is often highly expressed in colorectal cancer(CRC),but its role in this disease remains unclear.We demonstrated that PTPN18 overexpression promotes growth and tumorigenesis in CRC cells and that PTPN18 deficiency yields the opposite results in vitro.Moreover,a xenograft assay showed that PTPN18 deficiency significantly inhibited tumorigenesis in vivo.PTPN18 activated the MYC signaling pathway and enhanced CDK4 expression,which is tightly associated with the cell cycle and proliferation in cancer cells.Finally,we found that MYC interacted with PTPN18 and increased the protein level of MYC.In conclusion,our results suggest that PTPN18 promotes CRC development by stabilizing the MYC protein level,which in turn activates the MYC-CDK4 axis.Thus,PTPN18 could be a novel therapeutic target in the future.
基金
This work was supported by grants from the National Natural Science Foundation of China(NSFC)[grant numbers 81872271 and 81902844]
Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University[grant number ZNJC201921]
Zhongnan Hospital of Wuhan University Science,Technology and Innovation Seed Fund[grant number znpy2018102].