Caveolin‑1 enhances RANKL‑induced gastric cancer cell migration

Wang,Yan; Song,Yongxi; Che,Xiaofang; Zhang,Lingyun; Wang,Qian; Zhang,Xiaomeng; Qu,Jinglei; Li,Zhi; Xu,Ling; Zhang,Ye; Fan,Yibo; Hou,Kezuo; Liu,Yunpeng; Qu,Xiujuan

doi:10.3892/or.2018.6550

Caveolin‑1 enhances RANKL‑induced gastric cancer cell migration

Authors:
- Yan Wang
- Yongxi Song
- Xiaofang Che
- Lingyun Zhang
- Qian Wang
- Xiaomeng Zhang
- Jinglei Qu
- Zhi Li
- Ling Xu
- Ye Zhang
- Yibo Fan
- Kezuo Hou
- Yunpeng Liu
- Xiujuan Qu
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Affiliations: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: July 5, 2018 https://doi.org/10.3892/or.2018.6550
Pages: 1287-1296
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The classical pathway involving receptor activator of nuclear factor‑κB (RANK) and its ligand (RANKL) induces the activation of osteoclasts and the migration of a variety of tumor cells, including breast and lung cancer. In our previous study, the expression of RANK was identified on the surface of gastric cancer cells, however, whether the RANKL/RANK pathway is involved in the regulation of gastric cancer cell migration remains to be fully elucidated. Lipid rafts represent a major platform for the regulation of cancer signaling; however, their involvement in RANKL‑induced migration remains to be elucidated. To investigate the potential roles and mechanism of RANKL/RANK in gastric cancer migration and metastasis, the present study examined the expression of RANK by western blot analysis and the expression of caveolin‑1 (Cav‑1) in gastric cancer tissues by immunohistochemistry, in addition to cell migration which is measured by Transwell migration assay. The aggregation of lipid reft was observed by fluorescence microscopy and western blotting was used to measure signaling changes in associated pathways. The results showed that RANKL induced gastric cancer cell migration, accompanied by the activation of Cav‑1 and aggregation of lipid rafts. Nystatin, a lipid raft inhibitor, inhibited the activation of Cav‑1 and markedly reversed RANKL‑induced gastric cancer cell migration. The RANKL‑induced activation of Cav‑1 has been shown to occur with the activation of proto‑oncogene tyrosine‑protein kinase Src (c‑Src). The c‑Src inhibitor, PP2, inhibited the activation of Cav‑1 and lipid raft aggregation, and reversed RANKL‑induced gastric cancer cell migration. Furthermore, it was demonstrated that Cav‑1 was involved in RANKL‑induced cell migration in lung, renal and breast cancer cells. These results suggested that RANKL induced gastric cancer cell migration, likely through mechanisms involving the c‑Src/Cav‑1 pathway and lipid raft aggregation.

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