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Updated: Jan 20, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma
Zan Song1, Hao Dong1,2, Kailing Zhang1
1Institute of Immunopharmaceutical Sciences, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Abstract:
Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer with high mortality and limited therapeutic strategy. Glycine decarboxylase (GLDC) is the key limiting enzyme in glycine breakdown metabolism and acts as oncogene or tumor suppressor to impact tumor onset and progression in a context dependent manner. However, the underlying mechanism of GLDC on autophagy and progression is largely unexplored in HCC. Here, we showed that GLDC overexpression inhibited cell proliferation, cell migration and promoted cell senescence and autophagy in HCC. Intriguingly, induced GLDC remarkably attenuated epithelial-mesenchymal transition (EMT) progress and tumor growth in vitro and in vivo. Mechanically, we demonstrated that GLDC upregulated VPS34 protein and enhanced its interaction with VPS34, thus promoting the association of VPS34 with Beclin1/ATG14 complex and autophagy induction in HCC. Importantly, GLDC acetylation at K514 promoted interaction of GLDC-VPS34, whereas GLDC acetylation-dead mutant K514R abolished their binding. Furthermore, GLDC protein was decreased in HCC tissues compared with para-tumor tissues and reduced GLDC was significantly correlated with poor prognosis of patients. In conclusion, we unveil the key regulatory role of GLDC in autophagy and HCC progression through VPS34 and provide a potential strategy for HCC therapy.
Insights
Glycine decarboxylase (GLDC) suppresses hepatocellular carcinoma (HCC) by enhancing autophagy via VPS34 interaction. Reduced GLDC correlates with poor HCC prognosis, suggesting GLDC as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) presents high mortality with limited treatment options.
- Glycine decarboxylase (GLDC) has a context-dependent role in cancer, but its function in HCC progression and autophagy remains unclear.
Purpose of the Study:
- To investigate the role of GLDC in HCC progression, focusing on its impact on autophagy and epithelial-mesenchymal transition (EMT).
- To elucidate the molecular mechanism by which GLDC regulates autophagy in HCC.
Main Methods:
- Overexpression and knockdown of GLDC in HCC cell lines.
- Assessment of cell proliferation, migration, senescence, and autophagy.
- Analysis of epithelial-mesenchymal transition (EMT) markers.
- Co-immunoprecipitation assays to study protein interactions (GLDC, VPS34, Beclin1, ATG14).
- Analysis of GLDC acetylation at K514.
- Examination of GLDC expression in HCC patient tissues.
Main Results:
- GLDC overexpression inhibited HCC cell proliferation and migration, while promoting senescence and autophagy.
- Induced GLDC attenuated EMT and reduced tumor growth in vitro and in vivo.
- GLDC upregulated VPS34, enhancing its interaction with Beclin1/ATG14 complex to promote autophagy.
- GLDC acetylation at K514 was crucial for GLDC-VPS34 interaction.
- GLDC expression was decreased in HCC tissues and correlated with poor patient prognosis.
Conclusions:
- GLDC acts as a tumor suppressor in HCC by promoting autophagy through the VPS34-Beclin1/ATG14 pathway.
- GLDC acetylation is critical for its interaction with VPS34 and subsequent autophagy induction.
- Reduced GLDC levels in HCC tissues indicate its potential as a prognostic biomarker and therapeutic target for HCC.
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