[en] Cancer is one of the leading causes of death worldwide. In recent years, the number of studies investigating the involvement of fungi in carcinogenesis has significantly increased, and one of the most important ones is Candida albicans. Previously, the MicrobiomicsEHU research group observed that C. albicans promotes the malignant phenotype of melanoma cells and the overexpression of various genes related to the MAPK and HIF-1 signalling pathways. Based on this, the aim of this Master's Thesis was to delve deeper into the study of the changes induced by C. albicans in melanoma cells. To this end, the signalling pathways activated by the fungus in melanoma cells during co-incubation were analysed using molecular inhibitors. The secretion of the proangiogenic molecule VEGF by the cells was analysed using ELISA, and the expression of various proteins and genes were examined through Western blot and qPCR. The results showed that viable C. albicans strongly promoted VEGF secretion and the expression of c-Fos, a component of the AP-1 transcription factor. The initial response suggested that melanoma cells recognize the fungus through TLR and EphA2, which directly influence VEGF and c-Fos, respectively. Additionally, regarding metabolic pathways, it was described that VEGF synthesis and c-Fos expression are activated via p38 and HIF-1 pathways. When analysing the other possible components of AP-1, it was determined that these two pathways can regulate the expression of Atf3, Jun, and Jund, with Jund being the most prominent. Finally, the results related to metabolic reprogramming indicated that the genes Hk2, Slc2a1, and Eno2 can be regulated by the p38 pathway in the presence of the fungus. Overall, in melanoma cells, in the presence of C. albicans, MAPK/p38/c-Fos/AP-1 and HIF-1/HIF-1α/c-Fos/AP-1 pathways are important for creating a proangiogenic environment and for metabolic reprogramming. Therefore, the findings obtained in this work help to clarify the impact that Candida albicans may have on melanoma cells, which in the future could potentially enable the development of new therapies and treatments for melanoma cases caused or worsened by C. albicans.

[eu] Egun, minbizia mundu mailako heriotza-kausa nagusienetako bat da. Azken urteotan minbiziaren sorreran onddoek duten inplikazioa aztertzen duten ikerketa kopurua nabarmen hazi da, eta garrantzitsuenetariko bat Candida albicans da. Aurretiaz, MicrobiomicsEHU ikerketa taldean C. albicans-ek melanoma zelulen fenotipo gaiztoa eta MAPK eta HIF-1 seinalizazio bidezidorrekin loturiko hainbat generen gainadierazpena bultzatzen zuela ikusi zen. Hemendik abiatuta, Master Amaierako Lan honen helburua C. albicans-ek melanoma zeluletan eragiten dituen aldaketen azterketan sakontzea izan da. Horretarako, C. albicans melanoma zelulekin ko-inkubatzean onddoak melanoma zeluletan aktibatzen dituen bidezidorrak analizatu ziren, inhibitzaile molekularrez baliatuz. Zelulen VEGF molekula proangiogenikoaren jariapena ELISA bitartez analizatu zen, eta hainbat proteina zein generen adierazpenak Western blot eta qPCR bidez aztertu ziren. Lortutako emaitzetan bizirik zeuden C. albicans-ek VEGF-ren jariapena eta AP-1 transkripzio faktorea osatu dezakeen c-Fos-en adierazpena bortizki bultzatzen zutela erakutsi zuten. Erantzunarekin hasteko, melanoma zelulek onddoa TLR eta EphA2 bitartez ezagutu dezaketela ikusi zen, VEGF-ren eta c-Fos-en gainean eragin zuzena dutenak, hurrenez hurren. Gainera, bidezidor metabolikoei dagokienez, VEGF-ren sintesia eta c-Fos-en adierazpena p38 eta HIF-1 bidezidorren bitartez aktibatzen direla deskribatu zen. AP-1-en gainontzeko osagaiak aztertzean, aipaturiko bi bidezidorrek Atf3, Jun, eta Jund-ren adierazpenak erregulatu ditzaketela zehaztu zen, gehien bat Jund-rena. Azkenik, birprogramazio metabolikoarekin loturiko emaitzek Hk2, Slc2a1, eta Eno2 geneak onddoaren presentzian soilik p38 bidezidorretik erregulatu daitezkeela erakutsi zuten, HIF-1 bidezidorrak ez baitzuen eraginik erakutsi. Osotasunean, melanoma zeluletan, C. albicans-en presentzian, ingurune proangiogenikoa sortzeko eta birprogramazio metabolikoa gertatzeko MAPK/p38/c-Fos/AP-1 eta HIF-1/c-Fos/AP-1 garrantzitsuak dira. Ondorioz, lan honetan lortutako emaitzek Candida albicans-ek melanoma zeluletan izan dezakeen eragina argitzen lagundu du eta, horrek etorkizunean C. albicans-en ondorioz sortutako edo larriagotutako melanoma kasuentzako terapia eta tratamendu berriak garatzea ahalbidetu lezake.