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Klotho is known as an anti-aging gene. We previously reported that the expression of Klotho is a postoperative prognostic factor for patients with lung large cell neuroendocrine carcinoma and lung small cell carcinoma. Recently, Klotho was shown to suppress the epithelial-mesenchymal transition (EMT). In the present study, we examined the association between the expression of Klotho and the regulation of EMT in lung squamous cell carcinoma. We immunohistochemically examined the expression of Klotho in patients with lung squamous cell carcinoma who had undergone surgical resection or photodynamic therapy. The immunohistochemical analysis showed that Klotho expression was observed not only in normal bronchial epithelial cells, but also in centrally located early lung cancers, which were all carcinomas in situ and were treated using PDT. However, in lung cancer patients with invasive and or advanced squamous cell carcinoma who had undergone a complete surgical resection, Klotho expression was observed in only 4 patients (13%). To elucidate the associations between the expression of Klotho and the expressions of EMT-related proteins, such as E-cadherin, N-cadherin, vimentin, and Snail, we transiently transfected GFP-Klotho plasmid DNA into the human squamous lung cancer cell line SQ5 and examined the expressions of these proteins of GFP-positive cells after sorting using flow cytometry. In SQ5 cells overexpressing GFP-Klotho, the expression of N-cadherin, which is a mesenchymal marker, was completely inhibited, compared with that in SQ5 cells transfected with the GFP vector. The overexpression of Klotho did not affect the regulation of either other mesenchymal markers (such as vimentin and Snail) or the regulation of an epithelial marker (E-cadherin). We concluded that the expression of Klotho was related to the degree of cancer invasiveness and that Klotho inhibits the expression of N-cadherin and regulates the EMT in lung cancer.

Klotho expression is correlated to molecules associated with epithelial‑mesenchymal transition in lung squamous cell carcinoma