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.

蛋白酪氨酸磷酸酶非受体 18 型 (PTPN18) 通常在结直肠癌 (CRC) 中高表达，但其在该疾病中的作用仍不清楚。我们证明 PTPN18 过表达促进 CRC 细胞的生长和肿瘤发生，而 PTPN18 缺乏在体外产生相反的结果。此外，异种移植试验表明 PTPN18 缺陷显着抑制了体内肿瘤发生. PTPN18 激活 MYC 信号通路并增强 CDK4 表达，这与癌细胞的细胞周期和增殖密切相关。最后，我们发现 MYC 与 PTPN18 相互作用并增加了 MYC 的蛋白质水平。总之，我们的结果表明 PTPN18 通过稳定 MYC 蛋白水平来促进 CRC 发展，从而激活 MYC-CDK4 轴。因此，PTPN18 可能成为未来的新治疗靶点。