CD133 mediates the TGF‑β1‑induced activation of the PI3K/ERK/P70S6K signaling pathway in gastric cancer cells

Zhu,Youlong; Kong,Feifei; Zhang,Caihua; Ma,Cheng; Xia,Hong; Quan,Bin; Cui,Huaixin

doi:10.3892/ol.2017.7163

CD133 mediates the TGF‑β1‑induced activation of the PI3K/ERK/P70S6K signaling pathway in gastric cancer cells

Authors:
- Youlong Zhu
- Feifei Kong
- Caihua Zhang
- Cheng Ma
- Hong Xia
- Bin Quan
- Huaixin Cui
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Affiliations: Department of Second Gastrointestinal Surgery, Xuzhou Central Hospital, School of Medicine, Southeast University, Xuzhou, Jiangsu 221000, P.R. China, Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China
Published online on: October 10, 2017 https://doi.org/10.3892/ol.2017.7163
Pages: 7211-7216
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cluster of differentiation (CD)133 has been reported to be involved in the activation of the extracellular signal‑regulated kinase (ERK) signaling pathway in different types of cancer cells. CD133 has been reported to be involved in the activation of the ERK signaling pathway in various cancer cells. Transforming growth factor (TGF)‑β1 has also been reported to mediate the activation of the ERK signaling pathway. In addition, TGF‑β1 has been previously shown to mediate the activation of the ERK signaling pathway. Hence, the present study investigated the function of CD133 in the TGF‑β1‑induced activation of the ERK/P70S6K signaling pathway in human gastric cancer (GC) cells. To this end, GC cell lines SGC7901 and MKN45 were treated with TGF‑β1. The expression of CD133, phospho‑ERK (p‑ERK) and phospho‑P70S6 kinase (p‑P70S6K) was upregulated in the cells treated with TGF‑β1, while the expression of ERK and P70S6K was not altered. To investigate whether CD133 is involved in the TGF‑β1‑induced activation of the ERK/P70S6K signaling pathway in GC cells, immunomagnetic cell sorting was employed to isolate CD133+ GC cells, and a CD133‑expression construct or CD133‑targeting small interfering ribonucleic acids were transfected into cells to modulate the expression of CD133. Subsequently, the expression of CD133, ERK, p‑ERK, P70S6K, and p‑P70S6K was analyzed by western blotting. The CD133+ cells displayed a high expression of p‑ERK and p‑P70S6K. Furthermore, SGC7901 GC cells were treated with U0126, an inhibitor of the ERK signaling pathway, to assess whether CD133 is upstream of ERK/P70S6K. The results showed that the expression of p‑ERK and p‑P70S6K was downregulated in the cells treated with U0126, while the expression of CD133 remained unaltered. The above preliminary results showed that CD133 likely mediates the TGF‑β1‑induced activation of the ERK/P70S6K signaling pathway in human GC cells. To further understand the mechanism of regulation of the ERK/P70S6K signaling pathway by CD133, the expression of CD133 was modulated by transfecting cells with CD133‑expression constructs or CD133‑targeting small interfering ribonucleic acids. Results indicated that overexpression and silencing of CD133 directly increased and decreased the expression of p‑ERK and p‑P70S6K, respectively. Therefore, we hypothesized that CD133 mediates the TGF‑β1‑induced activation of the PI3K/ERK/P70S6K signaling pathway in human GC cells.

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