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Expression and Role of CFTR in Human Esophageal Squamous Cell Carcinoma

Abstract

Background

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride (Cl) anion conducting channel, and its role in esophageal squamous cell carcinoma (ESCC) was examined in the present study.

Methods

Overexpression experiments were conducted on human ESCC cell lines following the transfection of a CFTR plasmid, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. A microarray analysis was performed to examine gene expression profiles. Fifty-three primary tumor samples collected from ESCC patients during esophagectomy were subjected to an immunohistochemical analysis.

Results

Transfection of the CFTR plasmid into the ESCC KYSE 170 and KYSE 70 cell lines suppressed cell proliferation, migration, and invasion and induced apoptosis. The microarray analysis showed the up-regulated expression of genes involved in the p38 signaling pathway in CFTR plasmid-transfected KYSE 170 cells. Immunohistochemical staining revealed a relationship between the CFTR expression pattern at the invasive front and the pN category. A relationship was also observed between the weak expression of CFTR at the invasive front and a shorter postoperative survival in a prognostic analysis.

Conclusions

The overexpression of CFTR in ESCC activated the p38 signaling pathway and was associated with a good patient prognosis. These results indicate the potential of CFTR as a mediator of and/or a biomarker for ESCC.

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Acknowledgment

This study was supported by Grants-in-Aid for Scientific Research (C) (17K10602, 17K10710, 18K08628, 18K08689, 19K09202, and 19K09182) and a Grant-in-Aid for Young Scientists (19K18160) from the Japan Society for the Promotion of Science.

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Correspondence to Atsushi Shiozaki MD, PhD.

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Matsumoto, Y., Shiozaki, A., Kosuga, T. et al. Expression and Role of CFTR in Human Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 28, 6424–6436 (2021). https://doi.org/10.1245/s10434-021-09752-y

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