Lung tumours run an oyster KAT2A circuit as a bowel mutation pattern loses its old causes
San Diego researchers separated a colorectal mutation signature in 2,616 tumours and inferred a DNA-repair origin. Lung adenocarcinoma cells run an oyster glycolysis switch. Yeast beta glucan retrained mouse marrow against tumours.
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A colorectal mutation pattern in 2,616 tumours from San Diego loses its old causes
Researchers at the University of California San Diego reanalysed 2,616 colorectal tumours from three independent cohorts and separated a mutational signature that had been treated as a blend of already known patterns. In a peer-reviewed Nature Communications paper, the signature appears relatively late in tumour development, and tumours that carry it hold more small insertions and deletions. The authors infer late errors in DNA repair from that late appearance and the extra small insertions and deletions. They found no known POLD1 or mismatch-repair gene defects and write that experiments are still needed to establish the cause. The analysis does not name the cause of any individual cancer. The signature held across all three datasets.[1]
Lung adenocarcinoma cells run an oyster circuit through KAT2A and HDAC5
A team at the Institute of Oceanology of the Chinese Academy of Sciences traced a metabolic switch that intertidal oysters use to survive heat and oxygen shortage, then found human lung adenocarcinoma cells running the same circuit to keep glycolysis, the sugar-burning pathway, switched on. The peer-reviewed study appeared in Proceedings of the National Academy of Sciences. The circuit runs from the enzymes KAT2 and class IIa HDACs to the glycolytic enzymes PGK1 and ALDOA. In the tumour cells KAT2A is turned up and HDAC5 turned down; both the proteasomal and the lysosomal routes that would normally break those two enzymes down are closed, and the enzymes remain active. Corresponding author Li Li notes that the daily oxygen and energy shortages of an intertidal oyster resemble conditions inside a tumour. The team used multi-omics analysis, gene editing and biochemical assays in oysters and in cultured human cells. No patients were involved; a tumour in a person could keep glycolysis on by another route.[2]
Yeast beta glucan at Trinity College Dublin retrained marrow against tumours
A Trinity College Dublin group fed mice yeast beta glucan for four to twelve weeks before exposing them to colorectal, skin and breast cancer cells. The fibre reprogrammed early immune cells in the bone marrow into a stronger, longer-lasting anti tumour response, according to a peer-reviewed study in Cell Reports. All of the work was done in mice, and the authors say the findings do not support taking a beta glucan supplement against cancer. The same supplement also reversed immune damage that persisted in obese mice even after they had lost weight, which the authors call trained haematopoiesis.[3]
