In the relentless quest to decipher the intricate relationship between microorganisms and cancer, recent groundbreaking research from the University of the Basque Country (EHU) has spotlighted a surprising microbial perpetrator: the fungus Candida albicans. Long understood as a benign constituent of the human microbiota—colloquially nestled within the oral cavity, skin, gastrointestinal tract, and vaginal environment—Candida albicans has sparked a revolutionary reconsideration concerning its role in oncogenesis, particularly melanoma, the deadliest form of skin cancer.
While viruses and bacteria have traditionally dominated the discourse on microbe-induced carcinogenesis, fungi have remained largely overlooked despite their ubiquitous presence within the human host. The International Agency for Research on Cancer (IARC) classifies thirteen microorganisms across viral, bacterial, and parasitic taxa as carcinogenic; however, the emerging evidence from the MicrobiomicsEHU research team, led by Dr. Leire Aparicio Fernández, fundamentally challenges this paradigm by implicating Candida albicans as a biological agent capable of enhancing melanoma aggressiveness through complex molecular pathways.
Candida albicans influences melanoma cells by orchestrating the activation of several critical intracellular signaling cascades, notably the p38 MAPK and HIF-1α pathways. These signaling routes are central to cellular stress responses and hypoxia-inducible adaptations, respectively. The fungal-interactions instigate metabolic reprogramming within malignant cells, promoting an environment conducive to tumor progression. Enhanced angiogenesis—the formation of new blood vessels—facilitates increased oxygen and nutrient supply, thereby empowering cancer cells with the metabolic flexibility to thrive and metastasize.
The research meticulously dissected the fungal impact on key hallmarks of melanoma biology, including cell migration, adhesion, and proliferation. Intriguingly, Candida albicans augmented the migratory and metastatic potential of melanoma cells without altering their proliferation rates, indicating selective modulation of cellular behavior that favors dissemination over local tumor expansion. This selective influence underscores a nuanced pathogenic role, revealing fungi as active contributors to the metastatic cascade rather than simply passenger organisms.
Delving deeper into the molecular dialogue, the activation of p38-MAPK—a signaling pathway involved in response to cellular stress—and HIF-1α—a master regulator of hypoxia responses—by Candida albicans transforms the tumor microenvironment. This transformation supports metabolic shifts that pivot cancer cells toward glycolysis and other alternate energy-generating pathways, hallmark features of tumor cell adaptation and survival under oxygen-deprived conditions. The resultant metabolic plasticity not only sustains tumor growth but also empowers malignancies to evade therapeutic interventions.
The revelations brought forth by this study herald the potential for novel therapeutic avenues. Traditional cancer treatments have predominantly focused on directly targeting cancerous cells; however, the identification of fungal involvement opens an unexplored front wherein antifungal therapies could serve as adjuvants. By inhibiting Candida albicans, it may be possible to disrupt the signaling nexus promoting melanoma progression, thereby attenuating tumor invasiveness and metastasis.
Dr. Aparicio underscores the necessity for broadened oncological frameworks that extend beyond the prototypical viral and bacterial models to incorporate fungal components of the microbiota. The presence of these eukaryotic microorganisms—and their capacity to modulate host-pathogen interactions biochemically—necessitates a paradigm shift towards integrative cancer biology that embraces the multifaceted contributions of the human mycobiome.
The implications of this research ripple beyond melanoma, prompting investigations into the potential role of Candida albicans in other carcinomas such as colorectal and gastrointestinal cancers. Given the heterogeneity among cancer types, understanding whether these fungal mechanisms are conserved or uniquely adapted across different tumor microenvironments holds vital significance for precision medicine.
The PhD work of Leire Aparicio-Fernández, under the guidance of Professors Aitziber Antoran-Diaz and Andoni Ramirez-Garcia, represents a convergence of immunological, microbiological, and oncological sciences, exemplifying the interdisciplinary approach necessary to unravel cancer’s complex etiology. Their affiliations with the Department of Immunology, Microbiology, and Parasitology and the Faculty of Pharmacy at EHU provide a robust framework fostering translational research.
As cancer remains a leading cause of mortality worldwide, with estimates attributing up to 18% of cases to infectious agents, the identification of fungi’s involvement introduces a critical layer of complexity. The work reminds the scientific community of the dynamic interplay between host and microbiota in disease progression, emphasizing the need for comprehensive therapeutic strategies that address the tumor microenvironment in its entirety.
In sum, this pioneering research elucidates a heretofore underappreciated role for Candida albicans in promoting melanoma aggressiveness through strategic activation of signaling pathways and metabolic reprogramming. The elucidation of these mechanisms not only enriches our understanding of cancer biology but also beckons innovative clinical interventions, potentially revolutionizing the management of melanoma and other fungal-associated malignancies.
Subject of Research: The role of the fungus Candida albicans in enhancing melanoma aggressiveness via activation of p38-MAPK and HIF-1α signaling pathways and metabolic reprogramming.
Article Title: Enhancement of melanoma aggressiveness via p38-MAPK, HIF-1α pathways, and metabolic reprogramming induced by Candida albicans
News Publication Date: 17-Nov-2025
Web References:
References:
Leire Aparicio-Fernandez et al., “Enhancement of melanoma aggressiveness via p38-MAPK, HIF-1α pathways, and metabolic reprogramming induced by Candida albicans,” Scientific Reports, DOI: 10.1038/s41598-025-24055-y
Image Credits: Egoi Markaida, University of the Basque Country (EHU)
Keywords: Melanoma cells, Skin cancer, Melanoma, Cancer, Fungi, Mycology
