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Correlation of Gli1 and HER2 expression in gastric cancer: Identification of novel target

Xinyu Shao1, Xiaoyi Kuai1, Zhi Pang1

  • 1The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215006, P.R. China.

Scientific Reports
|January 12, 2018
PubMed

Insights

Gli1 is highly expressed in gastric cancer and linked to shorter survival. Targeting Gli1 may improve outcomes, especially in patients resistant to HER2-targeted therapies like trastuzumab.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • HER2 is a standard treatment for gastric cancer, but resistance and negative expression limit its use.
  • Both Gli1 and HER2 are implicated in gastric cancer pathogenesis, but their relationship is not well understood.

Purpose of the Study:

  • To investigate the correlation between Gli1 and HER2 expression in gastric cancer.
  • To evaluate Gli1 as a prognostic factor and potential therapeutic target in gastric cancer.

Main Methods:

  • Analysis of Gli1 and HER2 expression in gastric cancer tissues.
  • Correlation studies and survival analysis (univariate and multivariate).
  • In vitro and in vivo experiments to assess the effect of Gli1 suppression and combined HER2/SMO inhibition.

Main Results:

  • Gli1 and HER2 are highly expressed and positively correlated in gastric cancer.
  • Gli1 expression is associated with shorter survival, regardless of HER2 status.
  • Gli1 and HER2 expression, along with venous invasion, are independent prognostic factors.
  • Gli1 suppression reduces cancer cell viability and migration.
  • HER2 may regulate Gli1 via the Akt-mTOR-p70S6K pathway; combined HER2 and SMO inhibition shows synergistic effects.

Conclusions:

  • Gli1 is a significant prognostic indicator in gastric cancer.
  • Gli1 represents a potential therapeutic target, particularly for HER2-targeted therapy-resistant gastric cancers.

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