FFAR1-and FFAR4-dependent activation of Hippo pathway mediates DHA-induced apoptosis of androgen-independent prostate cancer cells
- Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070 (China)
- The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170 (China)
Highlights: • DHA induces cell growth inhibition and apoptosis of human prostate cancer cells. • DHA promotes YAP phosphorylation in androgen-independent prostate cancer cell lines. • DHA induces cell growth inhibition and apoptosis of PC3 cells via YAP. • DHA promotes YAP phosphorylation via FFAR1/4-dependent activation of the Hippo pathway. Evidence indicates that diets enriched in Docosahexaenoic acid (DHA), a 22:6 n-3 polyunsaturated fatty acid, reduces the risk of prostate cancer, but the biochemical mechanisms are unclear. The Hippo pathway has been well established as a tumor suppressor pathway and is involved in many diverse biologic processes including cell growth, cell death, and organ size control in organisms. Here we showed that DHA induces cell growth inhibition and apoptosis of human androgen-independent prostate cancer cells dependent on the Hippo pathway. DHA inactivates YAP by promoting phosphorylation in androgen-independent prostate cancer cell lines, accompanied by increased YAP cytoplasm translocation. We also observed that DHA-induced YAP phosphorylation was reversed by both the LATS1 and MST1 siRNAs. Further experiments showed that the mechanism of DHA-induced YAP phosphorylation associated with FFAR1 and FFAR4. Down-regulation of FFAR1 and FFAR4 resulted in reduced YAP phosphorylation and reversed DHA-induced YAP phosphorylation. In addition, DHA-induced YAP phosphorylation was abolished by dominant negative Gαs and PKA inhibitor H-89. Overall, these findings define a mechanism by which FFAR1-and FFAR4-dependent activation of Hippo pathway mediates DHA-induced apoptosis of androgen-independent prostate cancer cells, thus providing a promising therapeutic target for prostate cancer.
- OSTI ID:
- 23125255
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 506, Issue 3; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP
Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells