2. Academic Validation
  3. Enhancement of melanoma aggressiveness via p38-MAPK, HIF-1α pathways, and metabolic reprogramming induced by Candida albicans

Enhancement of melanoma aggressiveness via p38-MAPK, HIF-1α pathways, and metabolic reprogramming induced by Candida albicans

  • Sci Rep. 2025 Nov 17;15(1):40227. doi: 10.1038/s41598-025-24055-y.
Leire Aparicio-Fernandez 1,  Nahia Cazalis-Bereicua 1,  Maialen Areitio 1,  Oier Rodriguez-Erenaga 1,  Lucia Abio-Dorronsoro 1,  Leire Martin-Souto 1,  Idoia Buldain 2,  Joana Márquez 3,  Aitor Benedicto 4,  Beatriz Arteta 3,  Nuria Macias-Cámara 5,  Monika Gonzalez 5,  Jose Ezequiel Martin Rodriguez 5,  Ana M Aransay 5 6,  Aize Pellon 5 7,  David L Moyes 7,  Juan Anguita 5 8,  Aitor Rementeria 1,  Aitziber Antoran 9,  Andoni Ramirez-Garcia 1
Affiliations

Affiliations

  • 1 Department of Immunology, Microbiology and Parasitology, Faculty of Sciences and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain.
  • 2 Department of Immunology, Microbiology and Parasitology, Faculty of Pharmacy, UPV/EHU, Vitoria-Gasteiz, Spain.
  • 3 Department of Cell Biology and Histology, Faculty of Medicine and Nursery, UPV/EHU, Leioa, Spain.
  • 4 Department of Cell Biology and Histology, Faculty of Pharmacy, UPV/EHU, Vitoria-Gasteiz, Spain.
  • 5 Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.
  • 6 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
  • 7 Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Science, King's College London (KCL), London, UK.
  • 8 Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
  • 9 Department of Immunology, Microbiology and Parasitology, Faculty of Sciences and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain. aitziber.antoran@ehu.eus.
PMID: 41249785 DOI: 10.1038/s41598-025-24055-y
Abstract

Recent studies have increasingly focused on the role of fungi, including Candida albicans, in carcinogenesis. Since C. albicans is a component of the human microbiota, particularly on the skin, we investigated its effect on the phenotype and signalling pathways of melanoma cells. Assays for migration, adhesion, angiogenesis, and hepatic metastasis showed that C. albicans promotes a more malignant phenotype in melanoma cells. At the transcriptomic level, C. albicans increased the expression of VEGF (Vegfa), and genes associated with MAPK and HIF-1 signalling pathways, and with aerobic glycolysis. Further in vitro analysis revealed that TLRs and EphA2 receptors are involved in the recognition of live C. albicans, stimulating VEGF secretion and expression of the AP-1 transcription factor component c-Fos through p38-MAPK and HIF-1α. These pathways also regulate the expression of Other AP-1 constituents such as Atf3, Jun, and Jund. Moreover, p38-MAPK regulates glycolytic genes like Hk2, Slc2a1, and Eno2. In conclusion, C. albicans activates the p38-MAPK/c-Fos/AP-1 and HIF-1/HIF-1α/c-Fos/AP-1 pathways in melanoma cells, promoting a pro-angiogenic environment and metabolic reprogramming. Therefore, this study clarifies the impact of C. albicans on melanoma cells, which can lead to the use of Antifungal therapies as complementary to traditional treatments for melanoma.

Keywords

Angiogenesis; Cancer; Candida; Melanoma; Metabolism; Metastasis.

Figures
Products
Inhibitors & Agonists
Other Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z