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PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET

Hongmei Dong1, Wan Lin2, Liang Du3

  • 1Institute 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.

Cancer Letters
|June 18, 2023
PubMed

Insights

Protein tyrosine phosphatase receptor-type O (PTPRO) suppresses esophageal squamous cell carcinoma (ESCC) metastasis by inhibiting MET signaling. Low PTPRO and high phosphorylated MET predict poor prognosis in ESCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase.
  • Epigenetic silencing of PTPRO via promoter hypermethylation is associated with various malignancies.
  • The role of PTPRO in esophageal squamous cell carcinoma (ESCC) metastasis requires elucidation.

Purpose of the Study:

  • To investigate the function of PTPRO in suppressing ESCC metastasis.
  • To elucidate the molecular mechanism by which PTPRO affects metastasis.
  • To evaluate PTPRO and phosphorylated MET (p-MET) as prognostic biomarkers for ESCC.

Main Methods:

  • Utilized cellular and animal models of ESCC.
  • Analyzed patient samples for PTPRO expression and MET phosphorylation.
  • Investigated the dephosphorylation activity of PTPRO on MET at specific tyrosine residues (Y1234/1235).

Main Results:

  • Demonstrated that PTPRO suppresses ESCC metastasis in preclinical models.
  • Identified PTPRO's mechanism of action: inhibition of MET-mediated metastasis via dephosphorylation of MET at Y1234/1235.
  • Found that patients with low PTPRO and high p-MET expression exhibit significantly poorer prognosis.

Conclusions:

  • PTPRO acts as a suppressor of ESCC metastasis.
  • PTPRO inhibits metastasis by dephosphorylating MET, a key mediator of metastasis.
  • The PTPROlow/p-METhigh status serves as an independent prognostic factor for ESCC patients.
Keywords:
Esophageal squamous cell carcinomaMETMetastasisPTPROTyrosine phosphatase

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