NFAT and IRF4 : the characterization of a new regulatory axis in SK-MEL-28 melanoma cell line
| dc.contributor | Ph.D. Program in Molecular Biology and Genetics. | |
| dc.contributor.advisor | Emre, Tolga. | |
| dc.contributor.author | Yıldız Ayhan, Nalan. | |
| dc.date.accessioned | 2025-04-14T13:53:58Z | |
| dc.date.available | 2025-04-14T13:53:58Z | |
| dc.date.issued | 2023 | |
| dc.description.abstract | Successful melanoma treatment is limited in late stages of the disease. Characterizing pathways involved in melanoma initiation and progression is therefore of importance. Calcium related pathways are of interest in cancer treatments and melanoma cells were shown to have active calcium signaling. Regulation of Nuclear Factor of Activated T-cells (NFAT) family of transcription factors (TFs), including NFAT4 (NFATc3) are calcium dependent and this TF is the scope of this study. Interferon Regulatory Factor 4 (IRF4) is another TF of interest with high expression in melanoma next to lymphoid cancers. Both TFs were first identified in immune cells with important roles in transcriptional regulation. To date, no study has linked NFAT4 and IRF4 functions in melanoma. Active calcium signaling in SK-MEL-28 cell line was investigated by immunofluorescence imaging of NFAT4 localization. Loss of NFAT4 or IRF4 resulted in decreased competitive fitness by GFP competition assay. Trypan blue exclusion assay resulted in decreased % of viable cells. Reduced colony formation potential was observed by crystal violet staining of colonies. Matrigel coated transwell assay resulted in decreased invasion upon NFAT4 loss. NFAT4 binding on IRF4’s proximal promoter was shown by ChIP-qPCR and additional qRT-PCR and western blot experiments showed transcriptional regulation of IRF4 transcription. NFAT4 and IRF4 expression in publicly available patient melanoma tissue sample with spatial gene expression showed similar patterns. All together, results of this study indicate an important role for the NFAT4-IRF4 axis that may be used as a fundamental for development of direct melanoma targets, combinatorial, or development of adjuvant therapy. | |
| dc.format.pages | xxiv, 114 leaves | |
| dc.identifier.other | Ph.D. Program in Molecular Biology and Genetics. TKL 2023 U68 PhD (Thes PRED 2023 E74 | |
| dc.identifier.uri | https://digitalarchive.library.bogazici.edu.tr/handle/123456789/21635 | |
| dc.publisher | Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2023. | |
| dc.subject.lcsh | Melanoma. | |
| dc.subject.lcsh | Interferon. | |
| dc.title | NFAT and IRF4 : the characterization of a new regulatory axis in SK-MEL-28 melanoma cell line |
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