LMX1A inhibits metastasis of gastric cancer cells through negative regulation of β-catenin

Cell Biol Toxicol. 2016 Apr;32(2):133-9. doi: 10.1007/s10565-016-9326-0. Epub 2016 Apr 9.


Previously, we reported that the LIM homeobox transcription factor 1, alpha (LMX1A) presented tumor-suppressing roles in gastric AGS cells. Here, we showed that LMX1A also inhibits metastasis-related behaviors including migration and invasion of gastric cancer cells. Mechanistic study revealed that the role of LMX1A was mediated by β-catenin, as knockdown of LMX1A upregulated the expression of β-catenin and knockdown of β-catenin reversed the effects of LMX1A silencing. β-catenin is essential for the activation of WNT signaling pathway. Indeed, knockdown of LMX1A activated the expressions of WNT signaling target genes T cell-specific transcription factor 4 (TCF4) and matrix metalloproteinase-7 (MMP7). What is more, the expression of LMX1A was negatively correlated with WNT signaling target genes in two datasets of human gastric cancer tissues. Thus, our study revealed an anti-metastatic role of LMX1A in gastric cancer which is mediated by the negative regulation of β-catenin signaling target genes.

Keywords: Gastric cancer; LMX1A; Metastasis; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Down-Regulation
  • Humans
  • LIM-Homeodomain Proteins / biosynthesis
  • LIM-Homeodomain Proteins / genetics*
  • LIM-Homeodomain Proteins / metabolism
  • Neoplasm Metastasis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Wnt Signaling Pathway
  • beta Catenin / metabolism


  • CTNNB1 protein, human
  • LIM-Homeodomain Proteins
  • LMX1A protein, human
  • Transcription Factors
  • beta Catenin