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

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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.

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Acknowledgment

This work is supported in part by the Natural Science Foundation of Shanghai (grant no. 134119b2600) and Natural Science Foundation of Minhang District (grant no. 2014MHZ062).

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Authors and Affiliations

  1. Department of Gastroenterology, Minghang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, China

    Li Feng & Wei Lian

  2. Department of Pathology, Minghang Hospital, Fudan University, Shanghai, 201199, China

    Yun Xie

  3. Clinical Laboratory, Minghang Hospital, Fudan University, Shanghai, 201199, China

    Zhen Zhao

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  1. Li Feng
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  2. Yun Xie
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  3. Zhen Zhao
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  4. Wei Lian
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Correspondence to Li Feng.

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Feng, L., Xie, Y., Zhao, Z. et al. LMX1A inhibits metastasis of gastric cancer cells through negative regulation of β-catenin. Cell Biol Toxicol 32, 133–139 (2016). https://doi.org/10.1007/s10565-016-9326-0

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  • DOI: https://doi.org/10.1007/s10565-016-9326-0

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