C-MET-dependent signal transduction mediates retinoblastoma growth by regulating PKM2 nuclear translocation.
Cell Biochem Funct
; 38(2): 204-212, 2020 Mar.
Article
in En
| MEDLINE
| ID: mdl-31729060
ABSTRACT
Mesenchymal epithelial transition (C-MET) factor overexpression has been found in many types of cancer and has served as an important molecular target for therapeutic intervention. However, the role of C-MET in retinoblastoma remains largely unclear. The present study aimed to investigate the potential role and mechanism of C-MET in Y79 retinoblastoma cells. We found that C-MET was highly expressed in Y79 retinoblastoma cells, and, in addition, the levels of C-MET were positively correlated with cell proliferation and retinoblastoma growth. Inhibition of C-MET suppressed Y79 retinoblastoma cell proliferation and tumour growth. Mechanistically, we showed that HGF-induced C-MET-dependent signal transduction resulted in ERK 1/2 phosphorylation, which subsequently promoted the nuclear translocation of PKM2. Nuclear PKM2 further interacted with histone H3 and contributed to C-MET-dependent cyclin D1 and c-Myc expression and cell proliferation. These findings highlight the role of C-MET in Y79 retinoblastoma cells and reveal a C-MET-dependent signal transduction mechanism. C-MET may be a potential therapeutic target for retinoblastoma. SIGNIFICANCE OF THE STUDY We demonstrated a new target of retinoblastoma, C-MET. C-MET-dependent signal transduction promotes Y79 retinoblastoma cell proliferation and tumour growth through ERK 1/2/PKM2/histone H3 signalling pathway. C-MET may be a potential target for retinoblastoma therapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retinoblastoma
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Thyroid Hormones
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Signal Transduction
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Carrier Proteins
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Gene Expression Regulation, Neoplastic
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Proto-Oncogene Proteins c-met
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Active Transport, Cell Nucleus
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Membrane Proteins
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Cell Biochem Funct
Year:
2020
Type:
Article