Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ
Zhen Wang1,2, Peng Liu1,2, Xin Zhou1,2
1Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Research
|March 3, 2017
Summary
Endothelin receptor A (ETAR) drives colon cancer growth by activating YAP/TAZ proteins. This pathway involves the Hippo tumor suppressor pathway, crucial for ETAR-driven tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Endothelin receptor A (ETAR) is implicated in promoting cancer development.
- The precise mechanisms by which ETAR contributes to tumor growth remain unclear.
- ETAR signaling is known to influence cell proliferation, migration, and survival.
Purpose of the Study:
- To elucidate the mechanism by which ETAR promotes colon tumorigenesis.
- To investigate the role of YAP/TAZ transcription coactivators in ETAR signaling.
- To determine the involvement of the Hippo tumor suppressor pathway in ETAR-mediated tumor growth.
Main Methods:
- Utilized colon cancer cell lines for experiments.
- Administered Endothelin-1 to stimulate ETAR.
- Assessed YAP/TAZ phosphorylation, nuclear localization, and transcriptional activity.
- Investigated the role of Gαq/11 and Rho GTPase signaling.
- Evaluated the requirement of YAP/TAZ activation for ETAR-induced tumorigenesis.
Main Results:
- Endothelin-1 treatment led to YAP/TAZ dephosphorylation and nuclear accumulation in colon cancer cells.
- ETAR stimulation resulted in transcriptional activation of YAP/TAZ.
- ETAR signaling suppressed the Hippo pathway via Gαq/11 and Rho GTPase.
- YAP/TAZ activation was essential for ETAR-induced colon cell proliferation, migration, and tumorigenesis.
Conclusions:
- ETAR promotes colon cancer progression through the activation of the YAP/TAZ axis.
- The Hippo tumor suppressor pathway is a key mediator of ETAR signaling in colon cancer.
- Targeting the ETAR-YAP/TAZ pathway may offer a therapeutic strategy for colon cancer.
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