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.
journal_name
Cell Biochem Functjournal_title
Cell biochemistry and functionauthors
Dai H,Zeng W,Luo Hdoi
10.1002/cbf.3464subject
Has Abstractpub_date
2020-03-01 00:00:00pages
204-212issue
2eissn
0263-6484issn
1099-0844journal_volume
38pub_type
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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journal_title:Cell biochemistry and function
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