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Title: The role of PPARβ/δ in melanoma metastasis
Authors: Lim, Jonathan Chee Woei
Kwan, Yuet Ping
Tan, Michelle Siying
Teo, Melissa Hui Yen
Chiba, Shunsuke
Wahli, Walter
Wang, Xiaomeng
Keywords: Peroxisome Proliferator–activated Receptor β/δ
DRNTU::Science::Biological sciences::Biochemistry
Issue Date: 2018
Source: Lim, J. C. W., Kwan, Y. P., Tan, M. S., Teo, M. H. Y., Chiba, S., Wahli, W., & Wang, X. (2018). The role of PPARβ/δ in melanoma metastasis. International Journal of Molecular Sciences, 19(10), 2860-. doi:10.3390/ijms19102860
Series/Report no.: International Journal of Molecular Sciences
Abstract: Background: Peroxisome proliferator–activated receptor (PPAR) β/δ, a ligand-activated transcription factor, is involved in diverse biological processes including cell proliferation, cell differentiation, inflammation and energy homeostasis. Besides its well-established roles in metabolic disorders, PPARβ/δ has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPARβ/δ’s role in tumour progression and metastasis remains controversial. Methods: In the present studies, the consequence of PPARβ/δ inhibition either by global genetic deletion or by a specific PPARβ/δ antagonist, 10h, on malignant transformation of melanoma cells and melanoma metastasis was examined using both in vitro and in vivo models. Results: Our study showed that 10h promotes epithelial-mesenchymal transition (EMT), migration, adhesion, invasion and trans-endothelial migration of mouse melanoma B16/F10 cells. We further demonstrated an increased tumour cell extravasation in the lungs of wild-type mice subjected to 10h treatment and in Pparβ/δ−/− mice in an experimental mouse model of blood-borne pulmonary metastasis by tail vein injection. This observation was further supported by an increased tumour burden in the lungs of Pparβ/δ−/− mice as demonstrated in the same animal model. Conclusion: These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.
ISSN: 1661-6596
DOI: 10.3390/ijms19102860
Rights: © 2018 The Author(s). Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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