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. 2022 Apr;76(2):203-215.
doi: 10.18926/AMO/63425.

Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells

Tomoya Masuda  1 , Hiroshi Tazawa  1   2 , Yuuri Hashimoto  1 , Takeshi Ieda  1 , Satoru Kikuchi  1 , Shinji Kuroda  1   2 , Kazuhiro Noma  1 , Yasuo Urata  3 , Shunsuke Kagawa  1   4 , Toshiyoshi Fujiwara  1
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Free article

Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells

Tomoya Masuda et al. Acta Med Okayama. 2022 Apr.
Free article

Abstract

The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression.

Keywords: E1A; EMT; TGF-β; esophageal cancer; oncolytic adenovirus.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

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