PCNP promotes ovarian cancer progression by accelerating β-catenin nuclear accumulation and triggering EMT transition

J Cell Mol Med. 2020 Jul;24(14):8221-8235. doi: 10.1111/jcmm.15491. Epub 2020 Jun 16.

Abstract

Ever reports showed that PCNP is associated with human cancers including neuroblastoma and lung cancer. However, the role and underlying molecular mechanism of PCNP in ovarian cancer have not been plenty elucidated. Herein, we first investigated the expression of PCNP in ovarian cancer tissues and cells, the effects of PCNP in ovarian cancer proliferation, apoptosis, migration and invasion, and determined the molecular mechanism of PCNP in ovarian cancer progression. The results indicated that PCNP was significantly overexpressed in human ovarian cancer tissues and cells, and related to poor prognosis in ovarian cancer patients. In addition, we also detected that PCNP promoted ovarian cancer cells growth, migration and invasion, as well as inhibited ovarian cancer cells apoptosis. Mechanistically, PCNP binding to β-catenin promoted β-catenin nuclear translocation and further activated Wnt/β-catenin signalling pathway. Moreover, PCNP regulated the expression of genes involved in EMT and further triggered EMT occurrence. Conclusionally, PCNP may promote ovarian cancer progression through activating Wnt/β-catenin signalling pathway and EMT, acting as a novel and promising target for treating ovarian cancer.

Keywords: PEST-containing nuclear protein; Wnt; epithelial-mesenchymal transition; migration; ovarian cancer; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Disease Models, Animal
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Mice
  • Models, Biological
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Nuclear Proteins
  • PCNP protein, human
  • beta Catenin