Downregulation of STRAP promotes tumor growth and metastasis in hepatocellular carcinoma via reducing PTEN level

IUBMB Life. 2018 Feb;70(2):120-128. doi: 10.1002/iub.1707. Epub 2017 Dec 28.

Abstract

The serine-threonine kinase receptor-associated protein (STRAP) has been implicated in multiple human cancers. However, its expression and function are currently unclear and controversial in different tissue types. In the present study, we report that aberrant downregulation of STRAP in hepatocellular carcinoma (HCC) facilitated tumor cell growth and metastasis in a phosphatase and tensin homologue (PTEN)-dependent manner. Immunohistochemical analysis and quantitative real-time polymerase chain reaction results indicated that STRAP was frequently downregulated in HCC samples. Functionally, knockdown of STRAP by RNA inference in HCC cells promoted proliferation and migration in vitro and tumorigenicity and lung metastasis in vivo. Through detecting the expression of some tumor-related genes using western blot analysis, we found the tumor suppressor PTEN was decreased upon STRAP silencing. Further analyses demonstrated that silenced STRAP led to PTEN protein degradation. Immunohistochemical analysis revealed that STRAP expression was closely associated with PTEN expression in 30 cases of HCC samples. These findings strongly suggest that STRAP plays an inhibitory role in HCC via regulating PTEN expression and could be a potential therapeutic target for this disease. © 2017 IUBMB Life, 70(2):120-128, 2018.

Keywords: PTEN; STRAP; hepatocellular carcinoma; metastasis; tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice, Inbred BALB C
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • RNA-Binding Proteins
  • Xenograft Model Antitumor Assays

Substances

  • Neoplasm Proteins
  • RNA-Binding Proteins
  • STRAP protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human