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Updated: Aug 6, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Dual-faced metabolic reprogramming powers proliferation: FGF21 drives lung squamous carcinoma progression via
Xiao-Xin Pu1, Yan Zhang2, Bao-Yi Liu1
1Department of Pulmonary and Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.
Abstract:
Fibroblast growth factor 21 (FGF21) is upregulated in lung squamous cell carcinoma (LUSC) tissues, cell lines, and tumor-conditioned media. Functional studies using LUSC cell lines (H1703, H520) demonstrate that FGF21 promotes cancer cell proliferation, migration, invasion, and tumor sphere formation in vitro. This pro-tumorigenic effect was validated in vivo through xenograft models, where intra-tumoral FGF21 administration accelerated tumor growth. Mechanistically, FGF21 activates calcium/calmodulin-dependent protein kinase II (CaMKII), which phosphorylates dynamin-related protein 1 (DRP1, encoded by DNM1L) at Ser616. Phosphorylated DRP1 translocates to mitochondria, inducing mitochondrial fission. Metabolic analyses revealed that FGF21 remodels cellular energetics in a cell type-specific manner, enhancing glycolysis in H520 cells and oxidative phosphorylation (OXPHOS) in H1703 cells, consistent with their inherent predominant metabolic states. Knockdown of DRP1 or pharmacological inhibition of CaMKII (KN93) abolished FGF21-driven mitochondrial fission, metabolic reprogramming, and tumor-promoting effects. Collectively, FGF21 acts as a tumor-promoting factor in LUSC by activating the CaMKII/DRP1-Ser616 axis to induce pathological mitochondrial fission and metabolic reprogramming, identifying this pathway as a potential therapeutic target.
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