PRL-3 promotes migration and invasion and is associated with poor prognosis in salivary adenoid cystic carcinoma

J Oral Pathol Med. 2016 Feb;45(2):111-8. doi: 10.1111/jop.12331. Epub 2015 Jun 3.

Abstract

Background: PRL-3 had been found to be involved in tumorigenesis in various malignancies. In this study, we investigated the role of PRL-3 in the development, migration, and invasion of salivary adenoid cystic carcinoma (SACC).

Methods: Immunohistochemistry (IHC) was used to analyze the role of PRL-3 in the development and prognosis of SACC. Then, we overexpressed or inhibited the expression of PRL-3 in paired SACC cells to analyze the role of PRL-3 in the migration and invasion of SACC. In vitro migration and invasion assays were used. Western blotting was used to detect metastasis-related protein levels.

Results: IHC results confirmed that the deregulation of PRL-3 was a frequent event in SACC; the upregulation of PRL-3 was related to clinical stages, vital status, and distant metastasis, which was associated with reduced overall survival and disease-free survival. SACC-LM cells with higher migratory and invasive abilities had more robust PRL-3 protein expression than SACC-83 cells with lower migratory and invasive abilities. PRL-3 overexpression promoted cell migration, invasion, and proliferation, led to simultaneous upregulation of phosphorylated PRL-3, pERK1/2, Slug, vimentin, and downregulation of E-cadherin in SACC-83 cells. However, the inhibition of PRL-3 by PRL-3 inhibitor or PRL-3 siRNA in SACC-LM cells inhibited cell migration, invasion, and proliferation, resulted in simultaneous downregulation of phosphorylated PRL-3, pERK1/2, Slug, vimentin, and upregulation of E-cadherin.

Conclusions: Our results confirm that PRL-3 plays an important role in the development of SACC and contributes to the migratory and invasive abilities of SACC.

Keywords: PRL-3; invasion; migration; prognosis; salivary adenoid cystic carcinoma.

MeSH terms

  • Adult
  • Carcinoma, Adenoid Cystic / genetics
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Disease-Free Survival
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Phosphorylation
  • Prognosis
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology*

Substances

  • Neoplasm Proteins
  • RNA, Small Interfering
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases