Related Experiment Video

Updated: Oct 22, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

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

Published on: September 13, 2018

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Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2-Hippo signaling pathway

Yi Zhang1,2,3, Long-Jun He4, Lin-Lin Huang1,5

  • 1Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan 2nd Road, Guangzhou, 510630, China.

Clinical and Translational Medicine
|August 30, 2021
PubMed

Insights

PAX6 promotes gastric cancer progression and resistance to palbociclib by inactivating the Hippo pathway. Restoring Hippo signaling or using DNA methylation inhibitors can overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Intrinsic resistance to CDK4/6 inhibitors limits their effectiveness in cancer therapy.
  • Predictive biomarkers for CDK4/6 inhibitor response in gastric cancer (GC) are not fully understood.

Purpose of the Study:

  • To investigate the role of PAX6 in gastric cancer and its association with response to palbociclib.
  • To elucidate the molecular mechanisms underlying PAX6-mediated resistance to CDK4/6 inhibitors in GC.

Main Methods:

  • Correlation analysis of PAX6 expression with palbociclib response and patient survival in GC.
  • Investigating the effect of PAX6 on GC cell proliferation and cell cycle progression.
  • Assessing the impact of PAX6 on the Hippo pathway, LATS2 methylation, and cyclin D1 expression.
  • Evaluating strategies to overcome PAX6-induced palbociclib resistance.

Main Results:

  • PAX6 expression negatively correlated with palbociclib response and overall survival in GC patients.
  • PAX6 promotes GC cell proliferation and cell cycle progression.
  • PAX6 hypermethylates LATS2, inactivates the Hippo pathway, and upregulates cyclin D1, leading to palbociclib resistance.
  • Inducing the Hippo pathway or using DNA methylation inhibitors reversed PAX6-mediated palbociclib resistance.

Conclusions:

  • PAX6 acts as a tumor promoter in GC.
  • Overexpressed PAX6 is a novel mechanism of resistance to palbociclib in gastric cancer.
  • Targeting the PAX6/Hippo pathway axis offers potential therapeutic strategies for overcoming palbociclib resistance in GC.
Keywords:
CDK4/6 inhibitorDNA methylationHippo signaling pathwayPAX6

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