SARS-CoV-2 Modulates Lipid Metabolism in Colorectal Cancer Cells
MOREIRA I. 1, SOARES V. 1,2, WERNECK M. 1, DIAS S. 2, MASCARENHAS G. 1, CAMPOS M. 1, OLIVEIRA D. 1, ALVES M. 2, SOUZA T. 2, BASTOS N. 3, VIOLA J. 3, BOZZA P. 1,2
1 Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; 2 Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil; 3 Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil
Background: Colorectal cancer (CRC) progression is fundamentally driven by metabolic reprogramming, which enables tumor cells to sustain uncontrolled proliferation and adapt to hostile microenvironmental conditions. Among the altered metabolic pathways, lipid metabolism has emerged as a critical determinant of tumor aggressiveness, providing energy, membrane components, and lipid-derived signaling molecules that support tumor growth, survival, and immune modulation. Beyond cancer, lipid metabolism has also been identified as a key host dependency exploited by SARS-CoV-2 to facilitate viral entry, replication, and persistence, leading to substantial remodeling of cellular lipid homeostasis. This overlap strongly suggests that SARS-CoV-2 infection may amplify lipid metabolic reprogramming in colorectal cancer cells, and promote tumor progression and malignant behavior. However, the extent to which SARS-CoV-2–driven lipid metabolic alterations influence colorectal cancer development and progression remains unclear.
Objective: This study aimed to investigate the effects of SARS-CoV-2 infection on lipid metabolic remodeling in colorectal cancer cells and to explore its potential implications for tumor progression.
Methods: HCT116 colorectal carcinoma cells were cultured as 2D monolayers and infected with SARS-CoV-2 at multiplicities of infection (MOIs) of 0.01, 0.1, and 1. Cells were analyzed at 24, 48, and 72 hours post-infection. Cell death was assessed by lactate dehydrogenase (LDH) release assay, and viral replication was evaluated using plaque assays. Viral RNA presence was determined by RT-PCR, while lipid metabolic alterations were evaluated by gene and protein expression related to triglyceride and cholesterol biosynthesis pathways as well as intracellular lipid droplet detection.
Results: SARS-CoV-2 infection did not induce cytopathic effects or cell death, showing no significant increase in membrane damage compared to uninfected controls. Viral RNA was detected in infected cells at all time points; however, no increase in viral copy number was observed over time, indicating limited productive replication. Consistently, plaque assays confirmed the absence of infectious viral particle production, demonstrating that SARS-CoV-2 infection in these CRC cells is non-productive. Despite this lack of productive infection, the virus was able to induce a pronounced metabolic reprogramming: infected CRC cells exhibited significant accumulation of intracellular lipid droplets, accompanied by increased gene and protein expression of key enzymes, like SREBP, SCD, DGAT and PLIN2 involved in triglyceride and cholesterol synthesis pathways closely associated with tumor growth and metabolic adaptation.
Conclusions: Our findings demonstrate that SARS-CoV-2 infection promotes lipid metabolic reprogramming and increased lipid droplet accumulation in colorectal cancer cells independently of viral replication. Given the established role of lipid metabolism and lipid droplets in tumor progression, these virus-induced metabolic alterations may contribute to a tumor-supportive phenotype. This study highlights lipid metabolism as a critical interface between SARS-CoV-2 infection and colorectal cancer biology, providing new insights into how viral infections may influence cancer metabolism and progression.