Metastatic melanoma is an aggressive skin cancer that is notoriously resistant to current cancer therapies. Studies focused on the reciprocal interactions of melanoma and immune cells demonstrated that microenvironment-derived tumour necrosis factor (TNF-α) might induce dedifferentiation of the melanoma cells. Interleukin-8 (IL-8), a chemoattractant cytokine that has been demonstrated to positively influence tumour growth through autocrine and paracrine signalling is constitutively expressed in melanoma, however, it has remained not fully understand what factors elicit its upregulation since its expression can be regulated through a variety of mechanisms.
RIPK4 (Receptor-Interacting Protein Kinase 4) is a 91.6 kDa serine-threonine kinase belonging to the RIP family responsible for keratinocytes differentiation and stimulation of proinflammatory cytokine syntheses, such as CCL5, CXCL11 and IL8. RIPK4 is also involved in the regulation of the main signalling pathways in the cell, such as Wnt, NF-κB and acts as a “linker” between the PKC and NF-κB pathways. Constitutive activation of NF-κB pathway leads to the deregulation of gene transcription including IL-8 and plays a key role in the regulation of invasive properties and treatment resistance of melanoma.
Our studies show that RIPK4 level is manifold higher in melanoma cells than in normal melanocytes. Using interference siRNA technique we diminished the level of RIPK4 in melanoma cells and found that silencing of RIPK4 decrease activation of p65 and p-IKKα/β. Thus, we studied if IL-8 expression upon stimulation with TNF-α differs between melanoma cells with diminished level of RIPK4 expression and negative control (non-specific siRNA) by qRT-PCR and ELISA. We identified that IL-8 regulation by TNF-α in melanoma cell was mediated through RIPK4 and NF-κB activation.
The study was supported by the National Science Centre Grant number 2018/31/N/NZ3/02625 and 2018/31/B/N25/01423
I’m a PhD student in the Department of Biophysics. In my research I study signalling pathways in melanoma cells, focusing on the role of RIPK4 kinase in the regulation of melanoma cell invasiveness. I’m principal investigator in project “Engagement of RIPK4 in RAF1/MEK/ERK pathway in melanoma cells” funding by National Science Centre. Moreover recently I finished my project “Involvement of RIPK4 kinase in PKC/NFκB pathway in melanoma progression”, Grant was funded by KNOW 2018/2019 to Faculty of Biochemistry, Biophysics, and Biotechnology of Jagiellonian University.
Skalniak L, Smejda M, Cierniak A, Adamczyk A, Konieczny P, Madej E, Wolnicka-Głubisz
A. p38 but not p53 is responsible for UVA-induced MCPIP1 expression. Mech Ageing Dev. Volume 172, June 2018, Pages 96-106
1)XLV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Cracow, Zakopane, Poland, February 2018; The involvement of RIPK4 in the regulation of melanoma cell invasiveness (poster presentation)
2)IV Nationwide Biomedical Symposium Esculap, Lublin, Poland, December 2017; The receptor – interacting protein (RIP) kinase family as a new target in anticancer therapies (oral presentation)
3)17th Congress of the European Society for Photobiology, Pisa, Italy, September 2017; The role of p38/p53 in UVAinduced oxidative stress and MCPIP1 increase (author of the poster)
4)XLIV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Cracow, Zakopane, Poland, February 2017; The role of p53 in UVA- induced oxidative stress and MCPIP1 increase (poster presentation)