Title : Role of Glycanation and Convertase Maturation of Soluble
Glypican-3 in Inhibiting Proliferation of Hepatocellular Carcinoma Cells
Abstract :
- Glypican 3 ( GPC3 ) is a complex heparan sulfate proteoglycan associated with the outer surface of the plasma membrane by a glycosylphosphatidylinositol ( GPI ) anchor
- It is also N-glycosylated and processed by a furin-like convertase
- GPC3 has numerous biological functions
- Although GPC3 is undetectable in normal liver tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma (HCC)
- Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is inhibited when they express a soluble form of GPC3 after lentiviral transduction
- To obtain more insight into the role of some of its post-translational modifications, we designed a mutant GPC3 , sGPC3m , without its GPI anchor, convertase cleavage site , and glycosaminoglycan chains
- The highly pure sGPC3m protein strongly inhibited HuH7 and HepG2 cell proliferation in vitro and induced a significant increase in their cell doubling time
- It changed the morphology of HuH7 cells but not that of HepG2
- It induced the enlargement of HuH7 cell nuclear area and the restructuration of adherent cell junctions
- Unexpectedly, for both cell types, the levels of apoptosis, cell division, and β -catenin were not altered by sGPC3m , although growth inhibition was very efficient
- Overall, our data show that glycanation and convertase maturation are not required for sGPC3m to inhibit HCC cell proliferation
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 6. GPI, site
- 6. convertase, site
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):