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Liver X receptor activation reduces gastric cancer cell proliferation by suppressing Wnt signalling via LXRβ

Qiang Wang1, Fan Feng2, Jiayou Wang1

  • 1Institute of Life Sciences, Jiangsu University, Zhenjiang, China.

Journal of Cellular and Molecular Medicine
|October 20, 2018
PubMed

Insights

Liver X receptor beta (LXRβ) activation suppresses gastric cancer (GC) cell growth by inhibiting Wnt signaling. This research highlights LXRβ as a potential therapeutic target for GC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Liver X receptors (LXRs) are implicated in lipid disorders and cancer cell proliferation.
  • Molecular mechanisms of LXR action in gastric cancer (GC) require further elucidation.

Purpose of the Study:

  • To investigate the role and therapeutic potential of LXRβ in gastric cancer.
  • To elucidate the molecular pathways targeted by LXRβ activation in GC.

Main Methods:

  • Immunohistochemistry to assess LXRβ expression in GC tissues.
  • In vitro studies using GC cell lines treated with an LXRβ agonist (T0901317).
  • In vivo studies using a nude mouse xenograft model of GC.

Main Results:

  • LXRβ was predominantly expressed in GC tissues compared to normal adjacent tissues.
  • LXRβ agonist T0901317 inhibited GC cell proliferation and colony formation.
  • T0901317 induced LXRβ nuclear translocation, suppressing Wnt signaling and decreasing expression of target genes (MYC, BMP4, MMP7).
  • LXRβ agonist treatment suppressed GC tumor growth in vivo.

Conclusions:

  • LXRβ activation inhibits gastric cancer cell proliferation by suppressing Wnt signaling through LXRβ nuclear relocalization.
  • LXRβ represents a promising therapeutic target for gastric cancer treatment.
Keywords:
LXRβWnt signallingcell proliferationgastric cancertranslocation

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