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Irish Journal of Medical Science (1971 -)
Published in: Irish Journal of Medical Science (1971 -) 6/2023

05-04-2023 | Original Article

CCT6A promotes esophageal squamous cell carcinoma cell proliferation, invasion and epithelial-mesenchymal transition by activating TGF-β/Smad/c-Myc pathway

Authors: Xiuli Xia, Shushan Zhao, Wenting Chen, Chao Xu, Dongqiang Zhao

Published in: Irish Journal of Medical Science (1971 -) | Issue 6/2023

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Abstract

Objective

Chaperonin-containing TCP1 subunit 6A (CCT6A) facilitates several malignant cancer behaviors, but its regulation of esophageal squamous cell carcinoma (ESCC) has not been reported. This study aimed to investigate the effect of CCT6A on cell proliferation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) and its interaction with the TGF-β/Smad/c-Myc pathway in ESCC.

Methods

CCT6A expression was detected in ESCC and normal esophageal epithelial cell lines by RT‒qPCR and western blotting. Furthermore, CCT6A siRNA, negative control (NC) siRNA, CCT6A encoding plasmid and NC encoding plasmid were transfected into OE21 and TE-1 cells. Subsequently, CCT6A siRNA- and NC siRNA-transfected cells were treated with TGF-β for rescue experiments. Cell proliferation, apoptosis, invasion, and E-cadherin/N-cadherin and p-Smad2/p-Smad3/c-Myc expression were detected.

Results

CCT6A expression was increased in KYSE-180, TE-1, TE-4 and OE21 cells compared with HET-1A cells. In both OE21 and TE-1 cells, CCT6A knockdown inhibited cell proliferation, invasion and N-cadherin expression while promoting cell apoptosis and E-cadherin expression; meanwhile, CCT6A overexpression had the opposite effects. Furthermore, in both OE21 and TE-1 cells, CCT6A knockdown decreased p-Smad2/Smad2, p-Smad3/Smad3 and c-Myc/GAPDH expression; CCT6A overexpression had the opposite effects. Next, TGF-β facilitated cell proliferation, invasion, and N-cadherin, p-Smad2/Smad2, p-Smad3/Smad2 and c-Myc/GAPDH expression while repressing cell apoptosis and E-cadherin expression in OE21 and TE-1 cells; importantly, TGF-β could compensate for the regulation of CCT6A knockdown on these activities.

Conclusion

CCT6A facilitates ESCC malignant activities by activating the TGF-β/Smad/c-Myc pathway, which sheds light on the identification of a possible therapeutic target in the management of ESCC.
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Metadata
Title
CCT6A promotes esophageal squamous cell carcinoma cell proliferation, invasion and epithelial-mesenchymal transition by activating TGF-β/Smad/c-Myc pathway
Authors
Xiuli Xia
Shushan Zhao
Wenting Chen
Chao Xu
Dongqiang Zhao
Publication date
05-04-2023
Publisher
Springer International Publishing
Published in
Irish Journal of Medical Science (1971 -) / Issue 6/2023
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-023-03357-y

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