PTP1B up-regulates EGFR expression by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion in esophageal squamous cell carcinoma

Bei-Qing Pan; Zhi-Hui Xie; Jia-Jie Hao; Yu Zhang; Xin Xu; Yan Cai; Ming-Rong Wang

doi:10.1016/j.bbrc.2019.10.168

PTP1B up-regulates EGFR expression by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion in esophageal squamous cell carcinoma

Biochem Biophys Res Commun. 2020 Jan 29;522(1):53-60. doi: 10.1016/j.bbrc.2019.10.168. Epub 2019 Nov 15.

Authors

Bei-Qing Pan¹, Zhi-Hui Xie¹, Jia-Jie Hao¹, Yu Zhang¹, Xin Xu¹, Yan Cai¹, Ming-Rong Wang²

Affiliations

¹ 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.
² 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. Electronic address: wangmr2015@126.com.

PMID: 31735331
DOI: 10.1016/j.bbrc.2019.10.168

Abstract

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.

Keywords: EGFR; Esophageal squamous cell carcinoma; Invasion; MYH9; Migration; PTP1B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
ErbB Receptors / metabolism
Esophageal Neoplasms / metabolism*
Esophageal Squamous Cell Carcinoma / metabolism*
Gene Expression Regulation, Neoplastic*
Humans
Myosin Heavy Chains / chemistry*
Neoplasm Invasiveness
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*
Up-Regulation

Substances

MYH9 protein, human
EGFR protein, human
ErbB Receptors
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Myosin Heavy Chains