State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
Biochem Biophys Res Commun. 2020 Jan 29;522(1):53-60. doi: 10.1016/j.bbrc.2019.10.168. Epub 2019 Nov 15.
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Protein tyrosine phosphatase 1B (PTP1B) is a member of protein tyrosine phosphatases (PTPs) family. In our previous work, PTP1B was found to be overexpressed in ESCC tissues and made contributions to the the cell migration and invasion as well as lung metastasis of ESCC. In this study, we explored the underlying molecular mechanisms. PTP1B enhanced cell migration and invasion by promoting epidermal growth factor receptor (EGFR) expression in ESCC, which was relied on phosphatase activity of PTP1B. Using GST-pulldown combined with LC/MS/MS, we found that nonmuscle myosin IIA (MYH9) was a novel substrate of PTP1B in ESCC cells. PTP1B dephosphorylated MYH9 at Y1408, by which PTP1B up-regulated EGFR expression and enhanced cell migration and invasion in ESCC. In conclusion, our study first reported that PTP1B was the positive regulator of EGFR by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion, which revealed the regulatory mechanism of PTP1B-MYH9-EGFR axis in ESCC.
食管鳞状细胞癌 (ESCC) 是全球最常见的癌症之一。蛋白酪氨酸磷酸酶 1B (PTP1B) 是蛋白酪氨酸磷酸酶 (PTPs) 家族的一员。在我们之前的工作中，发现 PTP1B 在 ESCC 组织中过表达，并促进 ESCC 的细胞迁移、侵袭和肺转移。在这项研究中，我们探索了潜在的分子机制。PTP1B 通过促进 ESCC 中表皮生长因子受体 (EGFR) 的表达来增强细胞迁移和侵袭，这依赖于 PTP1B 的磷酸酶活性。通过 GST 下拉结合 LC/MS/MS，我们发现非肌肉肌球蛋白 IIA (MYH9) 是 ESCC 细胞中 PTP1B 的一个新的底物。PTP1B 在 Y1408 处使 MYH9 去磷酸化，从而上调 EGFR 的表达，并增强 ESCC 中的细胞迁移和侵袭。总之，我们的研究首次报道 PTP1B 通过去磷酸化 MYH9 的 Y1408 来负调控 EGFR，从而促进细胞迁移和侵袭，揭示了 PTP1B-MYH9-EGFR 轴在 ESCC 中的调控机制。
