Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

Int J Oncol. 2019 Mar;54(3):1086-1098. doi: 10.3892/ijo.2019.4674. Epub 2019 Jan 3.

Abstract

Globally, gastric cancer is the fifth most common malignancy, with high rates of incidence and mortality. The high mortality rate and poor prognosis of gastric cancer are closely associated with its profound invasiveness, high incidence of metastasis, rapid proliferation, and high rate of recurrence. Previous studies have confirmed that stathmin (STMN) has an important role in the occurrence, development and prognosis of gastric cancer. However, the detailed mechanisms by which STMN affects these processes remain unclear. The aim of the present study was to determine how STMN promotes invasion, migration and proliferation in gastric cancer tumor cells. The results of immunohistochemistry indicated that STMN is overexpressed in stomach neoplasm tissues, and that it is associated with migration, invasion, proliferation and anti‑apoptotic states of gastric cancer cells. The secretory proteins of gastric cancer cells with or without STMN knockdown were further analyzed using the isobaric tags for relative and absolute quantitation method to identify differentially expressed proteins verified by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Inhibition of STMN decreases the levels of clusterin, cystatin C and matrix metalloproteinases, followed by inhibiting the protein kinase B and signal transducer and activation of transcription activation. These findings suggest that STMN could be a promising therapeutic target for gastric cancer.

Keywords: gastric cancer; stathmin; isobaric tags for relative and absolute quantitation; clusterin; matrix metalloproteinases; protein kinase B; signal transducer and activation of transcription.

MeSH terms

  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Clusterin / genetics
  • Clusterin / metabolism*
  • Female
  • Gene Silencing*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / genetics*
  • Stathmin / genetics*
  • Stathmin / metabolism
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • CLU protein, human
  • Clusterin
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STMN1 protein, human
  • Stathmin
  • Proto-Oncogene Proteins c-akt