How lung tumors hijack an ancient marine metabolic axis to promote malignant growth
Researchers at the Institute of Oceanology of the Chinese Academy of Sciences (IOCAS) have shown how a metabolic mechanism underlying thermal tolerance in intertidal oysters sheds light on malignant proliferation in human lung adenocarcinoma.
Researchers from the Institute of Oceanology at the Chinese Academy of Sciences have discovered a fascinating connection between the metabolic mechanisms of intertidal oysters and the aggressive growth of lung adenocarcinoma. By studying how these marine invertebrates maintain energy production under harsh conditions, the scientists uncovered a metabolic axis called the KAT2/HDACIIa–PGK–ALDO, which helps the oysters adapt to stress.
Under energy stress, the balance between an acetyltransferase called KAT2 and a deacetylase called HDACIIa shifts, causing KAT2 to promote the acetylation of the glycolytic enzyme phosphoglycerate kinase (PGK). This modification stabilizes PGK and strengthens its interaction with another enzyme, aldolase (ALDO). As a result, PGK exhibits a noncanonical protein kinase activity that directly phosphorylates ALDO, boosting its catalytic efficiency and suppressing its degradation by the proteasome and lysosome.
The team found a striking similarity between this metabolic strategy in oysters and the Warburg effect in human tumors. Sessile intertidal oysters, which endure severe heat, aerial exposure, and hypoxia, have evolved a metabolic reprogramming toward aerobic glycolysis. The researchers then demonstrated that human lung cancer cells hijack this ancient stress-response axis by upregulating KAT2A and downregulating HDAC5.
This leads to persistent hyperacetylation of PGK1-K75 and hyperphosphorylation of ALDOA-S272, directly fueling malignant proliferation and metastasis in the tumor microenvironment.
The study's lead author, Dr. Wang Chaogang, noted that the oysters' extraordinary metabolic tolerance and adaptability make them a potential unconventional model organism to understand tumor metabolism better. Professor Li Li, the corresponding author of the study, emphasized that this research bridges marine evolutionary adaptation with human cancer metabolism.
By shedding light on the thermal adaptation strategies of marine invertebrates, the findings offer promising therapeutic targets for diagnosing and treating human malignancies.
Written by urgent.news from Medical Xpress's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
