{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:55:28Z","timestamp":1789563328557,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2018\/31\/N\/NZ3\/02625"],"award-info":[{"award-number":["2018\/31\/N\/NZ3\/02625"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["UMO-2018\/31\/B\/NZ5\/01423"],"award-info":[{"award-number":["UMO-2018\/31\/B\/NZ5\/01423"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The receptor-interacting protein kinase 4 (RIPK4) plays an important role in the development and maintenance of various tissues including skin, but its role in melanoma has not been reported. Using patient-derived cell lines and clinical samples, we show that RIPK4 is expressed in melanomas at different levels. This heterogenous expression, together with very low level of RIPK4 in melanocytes, indicates that the role of this kinase in melanoma is context-dependent. While the analysis of microarray data has revealed no straightforward correlation between the stage of melanoma progression and RIPK4 expression in vivo, relatively high levels of RIPK4 are in metastatic melanoma cell lines. RIPK4 down-regulation by siRNA resulted in the attenuation of invasive potential as assessed by time-lapse video microscopy, wound-healing and transmigration assays. These effects were accompanied by reduced level of pro-invasive proteins such as MMP9, MMP2, and N-cadherin. Incubation of melanoma cells with phorbol ester (PMA) increased PKC-1\u03b2 level and hyperphosphorylation of RIPK4 resulting in degradation of RIPK4. Interestingly, incubation of cells with PMA for short and long durations revealed that cell migration is controlled by the NF-\u03baB signaling in a RIPK4-dependent (RIPK4high) or independent (RIPK4low) manner depending on cell origin (distant or lymph node metastasis) or phenotype (mesenchymal or epithelial).<\/jats:p>","DOI":"10.3390\/ijms222111504","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T21:40:21Z","timestamp":1635198021000},"page":"11504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Deciphering the Functional Role of RIPK4 in Melanoma"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0729-0245","authenticated-orcid":false,"given":"Ewelina","family":"Madej","sequence":"first","affiliation":[{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics, Jagiellonian University, 7 Gronostajowa Street, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Ryszawy","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, 7 Gronostajowa Street, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-9965","authenticated-orcid":false,"given":"Anna A.","family":"Bro\u017cyna","sequence":"additional","affiliation":[{"name":"Faculty of Biological and Veterinary Sciences, Institute of Biology, Department of Human Biology, Nicolaus Copernicus University, 1 Lwowska Street, 87-100 Torun, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-4742","authenticated-orcid":false,"given":"Malgorzata","family":"Czyz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology of Cancer Lodz, Medical University of Lodz, 6\/8 Mazowiecka Street, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-7630","authenticated-orcid":false,"given":"Jaroslaw","family":"Czyz","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, 7 Gronostajowa Street, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-6349","authenticated-orcid":false,"given":"Agnieszka","family":"Wolnicka-Glubisz","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics, Jagiellonian University, 7 Gronostajowa Street, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21737","DOI":"10.1074\/jbc.M008069200","article-title":"Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase","volume":"276","author":"Chen","year":"2001","journal-title":"J. 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