APPL1 promotes the migration of gastric cancer cells by regulating Akt2 phosphorylation

Int J Oncol. 2017 Oct;51(4):1343-1351. doi: 10.3892/ijo.2017.4121. Epub 2017 Sep 5.


As a multifunctional adaptor protein, APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif 1) is overexpressed in many cancers, and has been implicated in tumorigenesis and tumor progression. The present study investigated the expression of APPL1 in gastric carcinoma and the function in regulating cell migration. We investigated the expression of APPL1 in gastric carcinoma based upon The Cancer Genome Atlas (TCGA) database. The expression of APPL1 in collected gastric carcinoma tissues and cultured cells was measured by qRT-PCR and western blot analysis. Transwell assay and wound healing assay were used to analyze the effects of APPL1 on tumor cell migration. The statistical results based upon TCGA database showed significantly higher expression of APPL1 in gastric carcinoma compared to adjacent normal tissues, and we confirmed these findings by measuring APPL1 expression in collected gastric carcinoma tissues and cultured cells. The results of transwell assay and wound healing assay showed that when APPL1 was silenced by siRNA, cell migration was inhibited and overexpression of APPL1 promoted migration. Western blot results demonstrated that changes in several mesenchymal markers were consistent with the observed reduction or enhancement of cell migration. Importantly, the expression of APPL1 significantly affected the phosphorylation of Akt2. In addition, MMP2 and MMP9, downstream effectors of Akt2 changed accordingly, which is a critical requirement for Akt2-mediated cell migration. The results demonstrate an important new function of APPL1 in regulating cell migration through a mechanism that depends on Akt2 phosphorylation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Up-Regulation


  • APPL1 protein, human
  • Adaptor Proteins, Signal Transducing
  • MIRN145 microRNA, human
  • MicroRNAs
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt