Iron depletion-induced downregulation of N-cadherin expression inhibits invasive malignant phenotypes in human esophageal cancer

Nishitani,Seishi; Noma,Kazuhiro; Ohara,Toshiaki; Tomono,Yasuko; Watanabe,Shinichiro; Tazawa,Hiroshi; Shirakawa,Yasuhiro; Fujiwara,Toshiyoshi

doi:10.3892/ijo.2016.3640

Iron depletion-induced downregulation of N-cadherin expression inhibits invasive malignant phenotypes in human esophageal cancer

Authors:
- Seishi Nishitani
- Kazuhiro Noma
- Toshiaki Ohara
- Yasuko Tomono
- Shinichiro Watanabe
- Hiroshi Tazawa
- Yasuhiro Shirakawa
- Toshiyoshi Fujiwara
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Affiliations: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, Shigei Medical Research Institute, Okayama, Japan
Published online on: July 29, 2016 https://doi.org/10.3892/ijo.2016.3640
Pages: 1351-1359

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Abstract

Esophageal carcinomas often have a poor prognosis due to early lymph node metastasis. Epithelial-mesenchymal transition (EMT) is strongly associated with the acquisition of cancer metastasis and invasion. However, there is no established treatment to eliminate the EMT of cancer cells. Iron is an essential element for both normal and cancer cells in humans. Recently, iron depletion has been discovered to suppress tumor growth. Therefore, we hypothesized that decreased iron conditions would regulate EMT phenotypes, as well as suppressing tumor growth. The human TE esophageal cancer cell lines and OE19 were used in our study. Decreased iron conditions were made using an iron-depletion diet in mice and the iron chelator deferasirox for cell studies. Migration and invasion abilities of cells were measured using migration, invasion, and sphere-formation assays. Esophageal subcutaneous tumor growth was suppressed in decreased iron conditions. In vitro study showed that decreased iron conditions inhibited esophageal cancer cell proliferation as well as migration and invasion abilities, with downregulation of N-cadherin expression. Also, migration and invasion abilities were suppressed by inhibiting expression of N-cadherin. In conclusion, decreased iron conditions revealed a profound anticancer effect by the suppression of tumor growth and the inhibition of migration and invasion abilities via N-cadherin.

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