High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer

Cell Death Dis. 2020 Aug 11;11(8):687. doi: 10.1038/s41419-020-02826-x.

Abstract

The prognosis for cervical cancer (CCa) patients with lymph node metastasis (LNM) is dismal. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa patients with LNM. However, the precise mechanism of LNM in CCa remains unclear. Herein, we demonstrated that protein tyrosine phosphatase receptor type M (PTPRM), identified from TCGA dataset, was markedly upregulated in CCa with LNM and correlated with LNM. Moreover, PTPRM was an independent prognostic factor of CCa patients in multivariate Cox's proportional hazards model analysis and associated with poor prognosis. Furthermore, through gain-of-function and loss-of-function approaches, we found that PTPRM promoted CCa cells proliferation, migration, invasion, lymphangiogenesis, and LNM. Mechanistically, PTPRM promoted epithelial-mesenchymal transition (EMT) via Src-AKT signaling pathway and induced lymphangiogenesis in a VEGF-C dependent manner, resulting in LNM of CCa. Importantly, knockdown of PTPRM dramatically reduced LNM in vivo, suggesting that PTPRM plays an important role in the LNM of CCa. Taken together, our findings uncover a novel molecular mechanism in the LNM of CCa and identify PTPRM as a novel prognostic factor and potential therapeutic target for LNM in CCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cholangiocarcinoma / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymph Nodes / metabolism
  • Lymphangiogenesis / genetics
  • Lymphatic Metastasis / genetics
  • Neoplasm Invasiveness / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism
  • Signal Transduction / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / physiopathology
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • Vascular Endothelial Growth Factor C
  • Phosphoric Monoester Hydrolases
  • PTPRM protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2