PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET

Hongmei Dong; Wan Lin; Liang Du; Zhimeng Yao; Feifei Li; Shuanglong Chen; Yiteng Huang; Hongzheng Ren; Yichen Luo; Songwang Cai; Yexi Chen; Hui Tang; Xiaofu Qiu; Yunlong Pan; Xingxu Huang; Dianzheng Zhang; Shegan Gao; Sai-Ching Jim Yeung; Hao Zhang

doi:10.1016/j.canlet.2023.216283

PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET

Cancer Lett. 2023 Jul 28:567:216283. doi: 10.1016/j.canlet.2023.216283. Epub 2023 Jun 17.

Authors

Hongmei Dong¹, Wan Lin², Liang Du³, Zhimeng Yao⁴, Feifei Li⁵, Shuanglong Chen⁶, Yiteng Huang⁷, Hongzheng Ren⁸, Yichen Luo⁶, Songwang Cai⁹, Yexi Chen¹⁰, Hui Tang¹¹, Xiaofu Qiu¹², Yunlong Pan¹³, Xingxu Huang¹⁴, Dianzheng Zhang¹⁵, Shegan Gao¹⁶, Sai-Ching Jim Yeung¹⁷, Hao Zhang¹⁸

Affiliations

¹ Institute of Precision Cancer Medicine and Pathology, And Department of Pathology, School of Medicine, And Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China; Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
² Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.
³ Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, China.
⁴ Institute of Precision Cancer Medicine and Pathology, And Department of Pathology, School of Medicine, And Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China; Department of Urology Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China.
⁵ Department of Oncology, People's Hospital of Leshan, Leshan, Sichuan, China.
⁶ Institute of Precision Cancer Medicine and Pathology, And Department of Pathology, School of Medicine, And Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China.
⁷ Health Care Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
⁸ Department of Pathology, Gongli Hospital, Naval Medical University, Shanghai, China; Department of Pathology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi, China.
⁹ Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
¹⁰ Department of General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
¹¹ Department of Central Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China; Department of Clinical Laboratory, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Heyuan, Guangdong, China.
¹² Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.
¹³ Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
¹⁴ MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, Jiangsu, China.
¹⁵ Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA.
¹⁶ College of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Henan Key Laboratory of Cancer Epigenetics, Luoyang, Henan, China. Electronic address: gsg112258@haust.edu.cn.
¹⁷ Department of Emergency Medicine, University of Texas MD Anderson Cancer Center and Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: syeung@mdanderson.org.
¹⁸ Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. Electronic address: haozhang@jnu.edu.cn.

PMID: 37331584
DOI: 10.1016/j.canlet.2023.216283

Abstract

Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase. Notably, epigenetically silenced PTPRO due to promoter hypermethylation is frequently linked to malignancies. In this study, we used cellular and animal models, and patient samples to demonstrate that PTPRO can suppress the metastasis of esophageal squamous cell carcinoma (ESCC). Mechanistically, PTPRO can inhibit MET-mediated metastasis by dephosphorylating Y1234/1235 in the kinase activation loop of MET. Patients with PTPRO^low/p-MET^high had significantly poor prognosis, suggesting that PTPRO^low/p-MET^high can serve as an independent prognostic factor for patients with ESCC.

Keywords: Esophageal squamous cell carcinoma; MET; Metastasis; PTPRO; Tyrosine phosphatase.

Publication types

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

MeSH terms

Animals
Cell Line, Tumor
Esophageal Neoplasms* / genetics
Esophageal Squamous Cell Carcinoma* / genetics
Lymphatic Metastasis
Phosphoric Monoester Hydrolases
Prognosis

Substances

Phosphoric Monoester Hydrolases