YEATS4 promotes the tumorigenesis of pancreatic cancer by activating beta-catenin/TCF signaling

Oncotarget. 2017 Apr 11;8(15):25200-25210. doi: 10.18632/oncotarget.15633.

Abstract

Beta-catenin/TCF signaling has been reported to promote the growth and metastasis of pancreatic cancer cells. However, the regulation for the beta-catenin/TCF transcriptional complex remains largely unknown. Here, we have found that YEATS4 is a positive regulator for Beta-catenin/TCF signaling. The expression of YEATS4 was elevated in clinical pancreatic cancer samples and pancreatic cancer mouse model. Up-regulation of YEATS4 promoted the growth, migration and invasion of pancreatic cancer cells, while knocking down the expression of YEATS4 inhibited the growth, migration, invasion and metastasis of pancreatic cancer cells. Moreover, the mechanism study revealed that YEATS4 interacted with beta-catenin and activated beta-catenin/TCF signaling. Furthermore, knocking down the expression of YEATS4 impaired the malignant transformation of normal pancreatic cells (HPDE6C7) by the oncogenic Ras. Taken together, our study demonstrated the oncogenic roles of YEATS4 in the progression of pancreatic cancer by activating beta-catenin/TCF signaling and suggested that YEATS4 might be a promising therapeutic target for pancreatic cancer.

Keywords: YEATS4; beta-catenin/TCF signaling; cancer metastasis; pancreatic cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Mice
  • Mice, Transgenic
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Signal Transduction*
  • TCF Transcription Factors / metabolism*
  • Transcription Factors / genetics*
  • Tumor Stem Cell Assay
  • beta Catenin / metabolism*

Substances

  • TCF Transcription Factors
  • Transcription Factors
  • YEATS4 protein, human
  • beta Catenin