Lysophosphatidic acid induces the migration and invasion of SGC-7901 gastric cancer cells through the LPA2 and Notch signaling pathways

Ren,Zhiheng; Zhang,Chenli; Ma,Linna; Zhang,Xiao; Shi,Shuxia; Tang,Deng; Xu,Jinyu; Hu,Yan; Wang,Binsheng; Zhang,Fangfang; Zhang,Xu; Zheng,Haixue

doi:10.3892/ijmm.2019.4186

Lysophosphatidic acid induces the migration and invasion of SGC-7901 gastric cancer cells through the LPA2 and Notch signaling pathways

Authors:
- Zhiheng Ren
- Chenli Zhang
- Linna Ma
- Xiao Zhang
- Shuxia Shi
- Deng Tang
- Jinyu Xu
- Yan Hu
- Binsheng Wang
- Fangfang Zhang
- Xu Zhang
- Haixue Zheng
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Affiliations: Department of Pathology, School of Basic Medicine, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Clinical Teaching Department of Lanzhou Modern Vocational College, Lanzhou, Gansu 730000, P.R. China, Department of Third General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730000, P.R. China
Published online on: May 8, 2019 https://doi.org/10.3892/ijmm.2019.4186
Pages: 67-78
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lysophosphatidic acid (LPA), a simple water‑soluble glycerophospholipid with growth factor‑like activity, regulates certain behaviors of multiple cancer types by binding to its receptor, LPA receptor 2 (LPA2). Notch1 is a key mediator in multiple human cancer cell types. The association between LPA2 and Notch1 in gastric cancer cells is not well known. The present study aimed to investigate the function of LPA2 and Notch1 in controlling the migration and invasion activities of SGC‑7901 gastric cancer cells following stimulation with LPA. It was revealed that LPA may stimulate the expression of Notch1 and Hes family bHLH transcription factor 1, and the phosphorylation of protein kinase B which belongs to the Notch pathway. Furthermore, by performing transwell migration and invasion assays, immunoﬂuorescent staining, analyzing the expression of markers for the epithelial‑mesenchymal transition (EMT) and downregulating LPA2 and Notch1 expression, it was verified that LPA2 and Notch1 mediated the metastasis, invasion, EMT and rebuilding of the cytoskeleton of SGC‑7901 cells upon LPA treatment. An immunoprecipitation assay revealed that LPA2 interacted with Notch1 in SGC‑7901 cells. The present study may provide novel ideas and an experimental basis for identifying the factors that affect the functions of SGC‑7901 cells.

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