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Akt signaling regulates the activities of lymphatic malformation endothelial cells through PKM2 nuclear translocation.

Created on 13 Sep 2026

Authors

Peipei Wang, Suyang Chen, Rong Wang, Guoyong Tong, Shaodong Yang, Wenqun Zhong, Yu Cai

Published in

Biochimica et biophysica acta. Molecular basis of disease. Pages 168462. Sep 12, 2026. Epub Sep 12, 2026.

Abstract

Lymphatic malformation (LM) is a developmental lymphatic anomaly characterized by abnormally activating lymphatic endothelial cells (LECs) and lymphangiogenesis. Recent studies have investigated that glycolysis can promote LM progression and pyruvate kinase M2 isoform (PKM2) is highly expressed in LM, whereas the mechanism involved remains unknown. In this study, we explored the mechanism for nuclear translocation of PKM2 in LECs isolated from LM (LM-LECs). Metabolic flux analyses, cell migration, cell invasion, and tube formation assays were performed to investigate the glycolysis level and activities of LM-LECs. A higher level of glycolysis was present in LM-LECs than that in human dermal lymphatic endothelial cells (HDLECs), which was associated with PKM2 expression, especially nuclear PKM2. Furthermore, inhibiting the nuclear translocation of PKM2 obviously restrained the activity of LM-LECs. Mechanistically, the data from RNA-seq and western blot showed that the level of nuclear PKM2 was regulated by PI3K-Akt pathway in LM-LECs. In sum, our results demonstrated that the PI3K-Akt signaling pathway was activated in LM-LECs, promoting the nuclear translocation of PKM2 and subsequently upregulating glycolysis levels in LM-LECs. Conversely, inhibition of the dimeric PKM2 significantly suppressed LM-LECs activity.

PMID:
42731735
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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