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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

Published on: September 13, 2018

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Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma

Keishi Sugimachi1, Miki Nishio, Shinichi Aishima

  • 1Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

Oncology
|April 28, 2017
PubMed
Abstract

Insights

Aberrant expression of Hippo pathway components, including YAP1 and MOB1, is linked to poor survival in intrahepatic cholangiocarcinoma (ICC). These findings highlight potential therapeutic targets for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Signaling Pathways

Background:

  • The Hippo signaling pathway, regulated by MOB1, is crucial for controlling cell proliferation.
  • Loss of MOB1 function in mice leads to intrahepatic cholangiocarcinoma (ICC).
  • The clinical relevance of the Hippo pathway in human ICC remains unclear.

Purpose of the Study:

  • To investigate the protein levels of key Hippo pathway components, YAP1 and MOB1, in human ICC.
  • To explore the role of the Hippo and TGF pathways in ICC pathogenesis.
  • To correlate protein expression with clinicopathological factors and patient prognosis.

Main Methods:

  • Analysis of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 protein levels in 88 ICC patient samples.
  • Quantification of protein expression using a scoring system.
  • Statistical analysis of protein levels against clinicopathological factors and overall survival.

Main Results:

  • Nuclear YAP1 overexpression (31.8%) correlated significantly with poor overall survival (p=0.01).
  • Decreased MOB1 expression (47.7%) was also associated with a poor prognosis (p=0.02).
  • High YAP1 levels were linked to SMAD2 nuclear localization, independent of TGFβ2, with high YAP1, low MOB1, and lymphatic permeation identified as independent risk factors for survival.

Conclusions:

  • Key components of the Hippo signaling pathway, YAP1 and MOB1, are frequently dysregulated in human ICC.
  • Aberrant expression of these proteins is associated with increased malignant potential and poorer patient outcomes.
  • These findings suggest that the Hippo pathway plays a significant role in ICC progression and may represent therapeutic targets.
Keywords:
Hippo pathwayIntrahepatic cholangiocarcinomaMOB1TGFβYAP1

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