Sustainability of CD24 expression, cell proliferation and migration, cisplatin-resistance, and caspase-3 expression during mesenchymal‑epithelial transition induced by the removal of TGF-β1 in A549 lung cancer cells

Kim,Seong‑Kwan; Park,Jin‑A; Zhang,Dan; Cho,Sang‑Hyun; Yi,Hee; Cho,Soo‑Min; Chang,Byung‑Joon; Kim,Jin‑Suk; Shim,Jae‑Han; Abd El‑Aty,A.  M.; Shin,Ho‑Chul

doi:10.3892/ol.2017.6398

Sustainability of CD24 expression, cell proliferation and migration, cisplatin-resistance, and caspase-3 expression during mesenchymal‑epithelial transition induced by the removal of TGF-β1 in A549 lung cancer cells

Authors:
- Seong‑Kwan Kim
- Jin‑A Park
- Dan Zhang
- Sang‑Hyun Cho
- Hee Yi
- Soo‑Min Cho
- Byung‑Joon Chang
- Jin‑Suk Kim
- Jae‑Han Shim
- A. M. Abd El‑Aty
- Ho‑Chul Shin
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Affiliations: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea, Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea, Natural Products Chemistry Laboratory, College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500‑757, Republic of Korea
Published online on: June 16, 2017 https://doi.org/10.3892/ol.2017.6398
Pages: 2410-2416

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Abstract

Epithelial-mesenchymal transition (EMT) is a notable mechanism underlying cancer cell metastasis. Transforming growth factor β1 (TGF‑β1) has been used to induce EMT; however, there is a lack of information regarding the role of TGF‑β1 in mesenchymal‑epithelial transition (MET). In the present study, EMT was induced in A549 lung cancer cells using TGF‑β1 (TGF‑β1‑treated group) and MET was induced sequentially from the TGF‑β1‑treated group by removing the TGF‑β1 (MET/return group). Untreated A549 lung cancer cells were used as a control. Characteristic features, including cancer stem cell markers [cluster of differentiation (CD)24, CD44 and CD133], cell proliferation and migration and diverse intracellular mechanisms, were observed in all groups. Using western blot analysis, the TGF‑β1‑treated group demonstrated increased vimentin and reduced E‑cadherin expression, whereas the MET/return group demonstrated the opposite trend. Among cancer stem cell markers, the population of CD24low cells was reduced in the TGF‑β1‑treated group. Furthermore, the G2/M phase cell cycle population, cisplatin‑sensitivity, and cell proliferation and migration ability were increased in the TGF‑β1‑treated group. These features were unaltered in the MET/return group when compared to the TGF‑β1‑treated group. Immunoblotting revealed an increase in the levels of SMAD3, phosphorylated SMAD3, phosphorylated extracellular signal‑regulated kinase and caspase‑3, and a decrease in active caspase‑3 levels in the TGF‑β1‑treated group. Increased caspase‑3 and reduced active caspase‑3 levels were observed in the MET/return group, similar to those in the TGF‑β1‑treated group; however, levels of other signalling proteins were unchanged compared with the control group. EMT induced by TGF‑β1 was not preserved; however, stemness‑associated properties (CD24 expression, caspase‑3 expression, cell proliferation and cisplatin‑resistance) were sustained following removal of TGF-β1.

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