Increased Lactate Dehydrogenase Activity Is Dispensable in Squamous Carcinoma Cells of Origin

January 2019 in “ Nature communications ”

Aimee Flores, S. Sandoval-Gonzalez, Rie Takahashi, Abigail S. Krall, Laila Sathe, Wei Liu, Caius G. Radu, James H. Joly, Nicholas A. Graham, Heather R. Christofk, William E. Lowry

lactate dehydrogenase A Ldha squamous cell carcinoma SCC hair follicle stem cells HFSCs glycolytic activity glutamine metabolism lactate dehydrogenase squamous carcinoma hair follicle cells glycolysis glutamine

Studysummary This study found that Ldh activity in hair follicle stem cell-mediated squamous cell carcinoma is not necessary for tumorigenesis, as its modulation did not affect the cancer's development or characteristics. Our plain-language summary of this paper — not a Tressless recommendation.

The study, involving 12 mice per genotype for tumor formation and progression quantification and 6 mice per genotype for Ldh activity assays, examined the necessity of lactate dehydrogenase A (Ldha) activity in the development and progression of squamous cell carcinoma (SCC) in a murine model. Despite the known high glycolytic activity in hair follicle stem cells (HFSCs) that initiate SCC, the researchers found that altering Ldha activity did not impact tumor initiation, growth, or progression. Even Ldha-null tumors, which had significantly reduced glycolytic metabolites and glucose uptake, were capable of forming SCC. The study also observed increased glutamine uptake and metabolism in Ldha-null tumors, suggesting metabolic flexibility and a potential compensatory mechanism for reduced glycolysis. These findings challenge the belief that high glycolytic activity is essential for SCC tumor growth and suggest that targeting both Ldh activity and glutamine metabolism might be a more effective therapeutic approach.