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Updated: Aug 25, 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

Published on: September 13, 2018

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The Impact of the Hippo Pathway and Cell Metabolism on Pathological Complete Response in Locally Advanced Her2+

Eriseld Krasniqi1, Francesca Sofia Di Lisa2, Anna Di Benedetto3

  • 1Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

Cancers
|October 14, 2022
PubMed

Insights

Low expression of cytoplasmic TAZ, YAP, HMGCR, and high SCD1 predicts residual disease in Her2+ breast cancer. This finding requires further validation in larger prospective studies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The Hippo pathway, involving Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), is frequently altered in breast cancer.
  • Cell metabolism regulators like AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) influence TAZ/YAP activity.

Purpose of the Study:

  • To investigate the association between Hippo pathway transducers (TAZ, YAP) and metabolic regulators (AMPK, SCD1, HMGCR) expression and pathological complete response in Her2+ breast cancer patients undergoing neoadjuvant therapy.
  • To assess the predictive value of these markers for treatment outcomes.

Main Methods:

  • Prospective study measuring tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR via immunohistochemistry in 65 Her2+ breast cancer patients.
  • Univariate and multivariate logistic regression analyses were performed to evaluate predictive significance.
  • Machine learning was used to identify a composite signature.

Main Results:

  • Low cytoplasmic TAZ expression, alone or as part of a composite signature (low nuclear YAP, low HMGCR, high cytoplasmic SCD1), predicted residual disease in univariate analysis.
  • This association was not significant in the multivariate model adjusting for estrogen receptor status and BMI.
  • Findings showed concordance with overall survival data from the TCGA cohort.

Conclusions:

  • The expression of TAZ, YAP, SCD1, and HMGCR may play a role in predicting treatment response in Her2+ breast cancer.
  • The predictive value of these markers requires further investigation in larger, prospective studies due to the current study's sample size limitations.
Keywords:
Her2−positive breast cancerHippo pathwaycell metabolismpathological complete response

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