RAP1B, a DVL2 binding protein, activates Wnt/beta-catenin signaling in esophageal squamous cell carcinoma

Gene. 2017 May 5:611:15-20. doi: 10.1016/j.gene.2017.01.021. Epub 2017 Jan 21.

Abstract

RAP1B is a small GTPase, which regulates multiple cellular processes. Up-regulation of RAP1B has been observed in several cancer types. Although previous study has shown that miR-518 inhibited the proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells possibly by targeting RAP1B, the expression pattern and the functions of RAP1B in ESCC are not fully understood. Here, we have fund that the expression of RAP1B was up-regulated in ESCC clinical samples. Gain-of-function and loss-of-function assays demonstrated that RAP1B promoted the growth, migration and metastasis of the ESCC cells. Moreover, the mechanism study showed that RAP1B interacted with DVL2, an important upstream regulator for beta-catenin/TCF signaling, and activated beta-catenin/TCF signaling. Taken together, our study demonstrated the oncogenic roles of RAP1B in ESCC, and suggested that RAP1B might be a therapeutic target.

Keywords: Beta-catenin/TCF signaling; Cell growth and migration; ESCC; RAP1B.

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dishevelled Proteins / genetics
  • Dishevelled Proteins / metabolism*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Mice, Nude
  • Neoplasm Metastasis
  • Protein Binding
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism*
  • rap GTP-Binding Proteins / genetics
  • rap GTP-Binding Proteins / metabolism*

Substances

  • DVL2 protein, human
  • Dishevelled Proteins
  • beta Catenin
  • RAP1B protein, human
  • rap GTP-Binding Proteins