Defining Metabolic Flexibility in Hair Follicle Stem Cell Induced Squamous Cell Carcinoma

The study explored the metabolic adaptability of hair follicle stem cell (HFSC) induced squamous cell carcinoma (SCC) in mice by genetically inhibiting key metabolic pathways. It was found that individually blocking glycolysis or glutaminolysis did not prevent tumor development, as SCC cells compensated by upregulating alternative metabolic pathways. Specifically, when glutaminase (GLS) was deleted, SCC cells increased lactate consumption to fuel the tricarboxylic acid (TCA) cycle. Additionally, the study observed post-transcriptional regulation of lactate and glutamine transporters in response to metabolic pathway inhibition. However, simultaneous blocking of both glycolysis and glutaminolysis pathways hindered the development of SCC, indicating a limit to the metabolic flexibility of these cancer cells. These results suggest that effective cancer treatments may need to target multiple metabolic pathways to overcome the adaptability of cancer cell metabolism.