Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator Snail in cholangiocarcinoma.
Epithelial-mesenchymal transition (EMT) is a series of events during which epithelial cells lose many of their epithelial characteristics and take on properties that are typical of mesenchymal cells that lack cell-cell adhesion properties. EMT may be activated by various types of growth factors or inflammatory cytokines. In many types of epithelial cancers, the EMT-derived tumor cells are susceptible to metastasis. During tumor progression, epithelial cells acquire a gene expression pattern closely resembling that of mesenchymal cells. This study aimed to investigate the expression of the EMT-associated transcription factor Snail and an adhesion molecule E-cadherin in cholangiocarcinoma (CCA) tissues. The effect of TNF-α on EMT activation in CCA cells was also demonstrated. The qRT-PCR analysis revealed that Snail expression significantly increased in CCA (P = 0.01) and was correlated with tumor metastasis (P = 0.02). The expression of Snail was inversely associated with E-cadherin (P = 0.004). The stimulation of TNF-α enhances migration behavior and showed significantly induced expression of Snail in CCA cell lines, whereas expression of E-cadherin and CK-19 (the epithelial marker) was reduced. Immunofluorescence analysis revealed that TNF-α-treated CCA cell lines increased nuclear translocation of Snail, whereas E-cadherin was dramatically decreased. Our findings suggest that the changes in the expression of Snail or E-cadherin might regulate EMT development in CCA resulting in promoting tumor progression. Overexpression of Snail could be used as a prognostic marker for monitoring the treatment efficiency of CCA patients.
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Anchalee
A
Techasen
Nisana
N
Namwat
Watcharin
W
Loilome
Pornpan
P
Bungkanjana
Narong
N
Khuntikeo
Anucha
A
Puapairoj
Patcharee
P
Jearanaikoon
Hideyuki
H
Saya
Puangrat
P
Yongvanit
D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha