title: LMX1A inhibits metastasis of gastric cancer cells through negative regulation of β-catenin.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Minghang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, China. mhfengli2016@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pathology, Minghang Hospital, Fudan University, Shanghai, 201199, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Clinical Laboratory, Minghang Hospital, Fudan University, Shanghai, 201199, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Minghang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lian
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; D014157:Transcription Factors; D051176:beta Catenin
keywords: Gastric cancer; LMX1A; Metastasis; β-catenin