PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer

作者：Min Ji, Heng-Chao Li, Zhiwei Cai, Xiao Yuan, Xi Pu, Yumeng Huang, Shengqiao Fu, Liangmei Chu, Chongyi Jiang, Junli Xue, Xiaoxin Zhang, Rongkun Li · 发表于：International Journal of Biological Sciences · 年份：2023 · DOI：10.7150/ijbs.76756 · 被引用次数：51 · 研究领域：Cancer, Hypoxia, and Metabolism、Pancreatic function and diabetes、Pancreatic and Hepatic Oncology Research

, while PYGL knockdown has opposite effects. Mechanically, hypoxia induces PYGL expression in a hypoxia inducible factor 1α (HIF1α)-dependent manner and promotes glycogen accumulation. Elevated PYGL mobilizes accumulated glycogen to fuel glycolysis via its activity as a glycogen phosphorylase, thus inducing the EMT process, which could be suppressed by the glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Clinically, PYGL expression is upregulated in PDAC and correlates with its malignant features and poor prognosis. Collectively, the data from our study reveal that the hypoxia/PYGL/glycolysis-induced EMT promotes PDAC metastasis, which establishes the rational for targeting hypoxia/PYGL/glycolysis/EMT signaling pathway against PDAC.