Cancer research (Chicago, Ill.), 2017-05, Vol.77 (9), p.2413-2423
2017
Details
- Autor(en) / Beteiligte
- Titel
- Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ
- Ist Teil von
- Cancer research (Chicago, Ill.), 2017-05, Vol.77 (9), p.2413-2423
- Ort / Verlag
- United States: American Association for Cancer Research, Inc
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Endothelin receptor A (ETAR) promotes tumorigenesis by stimulating cell proliferation, migration, and survival. However, the mechanism of ETAR in promoting tumor growth is largely unknown. In this study, we demonstrate that ETAR stimulates colon cell proliferation, migration, and tumorigenesis through the activation of YAP/TAZ, two transcription coactivators of the Hippo tumor suppressor pathway. Endothelin-1 treatment induced YAP/TAZ dephosphorylation, nuclear accumulation, and transcriptional activation in multiple colon cancer cells. ETAR stimulation acted via downstream G-protein Gαq/11 and Rho GTPase to suppress the Hippo pathway, thus leading to YAP/TAZ activation, which was required for ETAR-induced tumorigenesis. Overall, these results indicate a critical role of the YAP/TAZ axis in ETAR signaling. .
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.can-16-3229Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6724531
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Cancer, Carcinogenesis - genetics, Cell growth, Cell migration, Cell Movement - genetics, Cell proliferation, Cell Proliferation - genetics, Cell survival, Colon cancer, Colonic Neoplasms - genetics, Colonic Neoplasms - pathology, Colorectal cancer, Dephosphorylation, Endothelin 1, Endothelin-1 - administration & dosage, Endothelin-1 - genetics, Endothelins, Gene Expression Regulation, Neoplastic, GTP-Binding Protein alpha Subunits - genetics, Guanosine triphosphatases, HCT116 Cells, Humans, Intracellular Signaling Peptides and Proteins - genetics, Phosphoproteins - genetics, Receptor, Endothelin A - genetics, rho GTP-Binding Proteins - genetics, Signal transduction, Trans-Activators, Transcription activation, Transcription Factors, Tumor suppressor genes, Tumorigenesis, Yes-associated protein