{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:41:39Z","timestamp":1790098899412,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T00:00:00Z","timestamp":1537401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE2014-T2-1-036"],"award-info":[{"award-number":["MOE2014-T2-1-036"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore","award":["Start-up"],"award-info":[{"award-number":["Start-up"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Peroxisome proliferator\u2013activated receptor (PPAR) \u03b2\/\u03b4, 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, PPAR\u03b2\/\u03b4 has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPAR\u03b2\/\u03b4\u2019s role in tumour progression and metastasis remains controversial. Methods: In the present studies, the consequence of PPAR\u03b2\/\u03b4 inhibition either by global genetic deletion or by a specific PPAR\u03b2\/\u03b4 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 Ppar\u03b2\/\u03b4\u2212\/\u2212 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 Ppar\u03b2\/\u03b4\u2212\/\u2212 mice as demonstrated in the same animal model. Conclusion: These results indicated a protective role of PPAR\u03b2\/\u03b4 in melanoma progression and metastasis.<\/jats:p>","DOI":"10.3390\/ijms19102860","type":"journal-article","created":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T11:00:25Z","timestamp":1537527625000},"page":"2860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Role of PPAR\u03b2\/\u03b4 in Melanoma Metastasis"],"prefix":"10.3390","volume":"19","author":[{"given":"Jonathan Chee Woei","family":"Lim","sequence":"first","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore"},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuet Ping","family":"Kwan","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Siying","family":"Tan","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa Hui Yen","family":"Teo","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2039-023X","authenticated-orcid":false,"given":"Shunsuke","family":"Chiba","sequence":"additional","affiliation":[{"name":"Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-9089","authenticated-orcid":false,"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore"},{"name":"Center for Integrative Genomics, University of Lausanne, Le G\u00e9nopode, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Dr, Singapore 138673, Singapore"},{"name":"Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower Level 6, Singapore 169856, Singapore"},{"name":"Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5826\/dpc.0702a01","article-title":"Epidemiological trends in skin cancer","volume":"7","author":"Apalla","year":"2017","journal-title":"Dermatol. 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