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Updated: May 28, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

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Overexpression of SHANK2 contributes malignant outcomes as a Hippo pathway regulator in gastric cancer

Hiroshi Arakawa1, Shuhei Komatsu1, Jun Kiuchi1

  • 1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine Kyoto, Japan.

American Journal of Cancer Research
|February 14, 2025
PubMed
Abstract

Insights

SH3 and multiple ankyrin repeat domains 2 (SHANK2) promotes gastric cancer (GC) by suppressing the Hippo pathway. High SHANK2 expression indicates poor prognosis and suggests SHANK2 as a therapeutic target in GC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • SH3 and multiple ankyrin repeat domains 2 (SHANK2) is amplified in 11q13 and acts as a Hippo pathway suppressor in liver cancer.
  • Its role in gastric cancer (GC) remains largely unexplored.

Purpose of the Study:

  • To investigate the role of SHANK2 in gastric cancer (GC) development and progression.
  • To determine if SHANK2 acts as a cancer-promoting gene via activation or overexpression in GC.

Main Methods:

  • Analysis of SHANK2 expression in 5 GC cell lines and 172 primary GC tumor samples.
  • SHANK2 knockdown experiments to assess effects on cell proliferation, migration, and invasion.
  • Immunohistochemical analysis to correlate SHANK2 expression with clinical parameters and patient outcomes.

Main Results:

  • SHANK2 was overexpressed in 80% of GC cell lines.
  • SHANK2 knockdown inhibited GC cell proliferation, migration, and invasion, and induced Hippo pathway gene expression.
  • High SHANK2 index (cytoplasmic overexpression and low nuclear expression) correlated with aggressive clinicopathological features, advanced stage, and poor patient survival.
  • Multivariate analysis confirmed high SHANK2 index as an independent predictor of poor outcomes in GC.

Conclusions:

  • SHANK2 plays a significant role in promoting tumor malignancy in GC by suppressing the Hippo pathway.
  • SHANK2 serves as a valuable prognostic biomarker for GC.
  • SHANK2 represents a potential therapeutic target for gastric cancer treatment.
Keywords:
Hippo pathwaySHANK2gastric canceroverexpressionprognosis

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