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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
The Hippo pathway as a drug target in gastric cancer
Yiting Qiao1, Tongyu Li1, Shusen Zheng1
1The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, PR China.
Abstract:
The Hippo tumor suppressor pathway is critical for balancing cellular differentiation and proliferation in response to cell-cell contact, mechanical signals and diffusible signals such as lysophosphatidic acid. Hippo pathway signaling is frequently dysregulated in gastric cancer (GC), as well as many other kinds of solid tumors, contributing to multiple aspects of malignant progression including unchecked cell division and metastasis. Considering the importance of this Hippo pathway in cancer, its pharmacological disruption may be of huge benefit in the fight against this disease. In this review, we summarize the components of the Hippo pathway, its crosstalk with other major oncogenic signaling pathways, common mechanisms of its dysregulation, as well as potential therapeutic approaches of targeting this pathway for cancer treatment, specifically in a GC context.
Insights
The Hippo pathway regulates cell growth and is often disrupted in gastric cancer (GC). Targeting this pathway offers a promising therapeutic strategy for treating GC and other solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The Hippo tumor suppressor pathway is essential for maintaining cellular homeostasis by regulating cell differentiation and proliferation.
- Dysregulation of the Hippo pathway is implicated in the pathogenesis of various cancers, including gastric cancer (GC).
- Aberrant Hippo signaling contributes to uncontrolled cell division and metastasis in malignant tumors.
Purpose of the Study:
- To review the molecular components and signaling mechanisms of the Hippo pathway.
- To explore the crosstalk between the Hippo pathway and other oncogenic signaling cascades.
- To summarize the common dysregulation mechanisms of the Hippo pathway in cancer, particularly GC.
- To discuss potential therapeutic strategies targeting the Hippo pathway for cancer treatment.
Main Methods:
- Literature review of the Hippo pathway and its role in cancer.
- Analysis of signaling crosstalk with other oncogenic pathways.
- Examination of Hippo pathway dysregulation in gastric cancer.
- Identification and summary of therapeutic approaches targeting the Hippo pathway.
Main Results:
- The Hippo pathway's role in cell-cell contact, mechanical, and chemical signaling is crucial for normal tissue development.
- Hippo pathway components (e.g., LATS, YAP, TAZ) are frequently altered in GC, leading to oncogenic phenotypes.
- Crosstalk with pathways like Wnt/β-catenin and PI3K/Akt amplifies malignant progression.
- Pharmacological targeting of Hippo pathway components shows potential for cancer therapy.
Conclusions:
- The Hippo pathway is a critical regulator of cell proliferation and differentiation, and its dysregulation drives gastric cancer progression.
- Understanding the intricate signaling networks and dysregulation mechanisms of the Hippo pathway is key to developing effective cancer therapies.
- Targeting the Hippo pathway presents a promising avenue for novel therapeutic interventions against gastric cancer and other solid tumors.
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