Int J Mol Sci.: auth.: W.Wahli

 2018 Sep 20;19(10). pii: E2860. doi: 10.3390/ijms19102860.

The Role of PPARβ/δ in Melanoma Metastasis.

Lim JCW1,2Kwan YP3Tan MS4Teo MHY5Chiba S6Wahli W7,8Wang X9,10,11,12.



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.


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.


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.


These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.


EMT; invasion; melanoma; metastasis; migration; peroxisome proliferator–activated receptor β/δ

PMID: 30241392