We have located links that may give you full text access.
Downregulation of glycine decarboxylase enhanced cofilin-mediated migration in hepatocellular carcinoma cells.
Free Radical Biology & Medicine 2018 May 21
Metabolic reprogramming is a hallmark of cancer. Glycine decarboxylase (GLDC), an oxidoreductase, plays an important role in amino acid metabolism. While GLDC promotes tumor initiation and proliferation in non-small cell lung cancer and glioma and it was reported as a putative tumor suppressor gene in gastric cancer, the role of GLDC in hepatocellular carcinoma (HCC) is unknown. In the current study, microarray-based analysis suggested that GLDC expression was low in highly malignant HCC cell lines, and clinicopathological analysis revealed a decrease in GLDC in HCC tumor samples. While the knockdown of GLDC enhanced cancer cell migration and invasion, GLDC overexpression inhibited them. Mechanistic studies revealed that GLDC knockdown increased the levels of reactive oxygen species (ROS) and decreased the ratio of glutathione/oxidized glutathione (GSH/GSSG), which in turn dampened the ubiquitination of cofilin, a key regulator of actin polymerization. Consequently, the protein level of cofilin was elevated, which accounted for the increase in cell migration. The overexpression of GLDC reversed the phenotype. Treatment with N-acetyl-L-cysteine decreased the protein level of cofilin while treatment with H2 O2 increased it, further confirming the role of ROS in regulating cofilin degradation. In a tumor xenographic transplant nude mouse model, the knockdown of GLDC promoted intrahepatic metastasis of HCC while GLDC overexpression inhibited it. Our data indicate that GLDC downregulation decreases ROS-mediated ubiquitination of cofilin to enhance HCC progression and intrahepatic metastasis.
Full text links
Trending Papers
A Personalized Approach to the Management of Congestion in Acute Heart Failure.Heart International 2023
Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium-Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure.International Journal of Molecular Sciences 2024 Februrary 21
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app