Fibroblast activation protein-α promotes the growth and migration of lung cancer cells via the PI3K and sonic hedgehog pathways

Jia,Jun; Martin,Tracey A.; Ye,Lin; Meng,Lin; Xia,Nan; Jiang,Wen G.; Zhang,Xiaodong

doi:10.3892/ijmm.2017.3224

Fibroblast activation protein-α promotes the growth and migration of lung cancer cells via the PI3K and sonic hedgehog pathways

Authors:
- Jun Jia
- Tracey A. Martin
- Lin Ye
- Lin Meng
- Nan Xia
- Wen G. Jiang
- Xiaodong Zhang
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Affiliations: VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XW, UK, Department of Biochemistry and Molecular Biology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
Published online on: October 27, 2017 https://doi.org/10.3892/ijmm.2017.3224
Pages: 275-283
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A characteristic of the epithelial-to-mesenchymal transition in cancer cells is the upregulation of mesenchymal markers. Fibroblast activation protein α (FAPα) is predominantly expressed by stromal fibroblasts. Previous studies have demonstrated that FAPα is also expressed by certain epithelium-derived cancer cells and is involved in the regulation of certain signaling pathways. One of our previous studies showed that FAPα promoted the proliferation of breast cancer cells via the phosphatidylinositol-3-kinase (PI3K) signaling pathway. In the present study, the A549 adenocarcinoma (AC) and SK-MES-1 squamous cell carcinoma (SCC) lung cancer cell lines were transfected with FAPα. The FAPα-expressing SK-MES-1 cells exhibited an increased growth rate, whereas the FAPα-expressing A549 cells exhibited a similar growth rate, compared with respective empty vector‑transfected control cells. Electric cell-substrate impedance sensing (ECIS)-based attachment and wound-healing assays showed that the overexpression of FAPα markedly increased the adhesive and migratory properties of the SK-MES-1 cells but not those of the A549 cells. Additionally, inhibitors of focal adhesion kinase, agonist-induced phospholipase C, neural Wiskott‑Aldrich syndrome protein, extracellular signal‑regulated kinase, Rho-associated protein kinase, PI3K, and sonic hedgehog (SHH) were used to evaluate the interaction between FAPα and signaling pathways. Only the inhibitors of SHH and PI3K inhibited the increased motility of the FAPα‑expressing SK-MES-1 cells. Western blot analysis confirmed the activation of PI3K/AKT and SHH/GLI family zinc finger 1 signaling in the FAPα-expressing SK-MES-1 cells. These results revealed that FAPα promoted the growth, adhesion and migration of lung SCC cells. In addition, FAPα regulated lung cancer cell function, potentially via the PI3K and SHH pathways. Further investigations are required to examine the role of FAPα in lung AC cells.

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