Involvement of upregulation of fibronectin in the pro‑adhesive and pro‑survival effects of glucocorticoid on melanoma cells

Huang,Gao‑Xiang; Qi,Min‑Fang; Li,Xiao‑Long; Tang,Fang; Zhu,Lei

doi:10.3892/mmr.2017.8269

Involvement of upregulation of fibronectin in the pro‑adhesive and pro‑survival effects of glucocorticoid on melanoma cells

Authors:
- Gao‑Xiang Huang
- Min‑Fang Qi
- Xiao‑Long Li
- Fang Tang
- Lei Zhu
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Affiliations: Department of Pathology, No. 181 Hospital of People's Liberation Army, Guilin, Guangxi 541002, P.R. China, Department of Cardiology, Navy General Hospital, Beijing 100048, P.R. China, Department of Orthopedic Trauma Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
Published online on: December 12, 2017 https://doi.org/10.3892/mmr.2017.8269
Pages: 3380-3387

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Abstract

Glucocorticoids (GCs) are important stress hormones, which are used as a concomitant medication during malignant tumor chemotherapy. Clinical and preclinical studies have linked GCs to melanoma growth and progression. However, the effects and mechanism of action of GCs on the adhesion and survival of melanoma cells are still unknown. In the present study the effect of dexamethasone (Dex), a synthetic GC, on fibronectin (FN) expression and its roles in regulating the adhesion and survival of melanoma cells were investigated. It was revealed that Dex significantly increased the levels of intracellular and secreted FN in melanoma cell lines by increasing glucocorticoid receptor‑mediated FN protein stability. Additionally, it was demonstrated that Dex (100 nM) significantly promoted the adhesion and survival of melanoma cells. Silencing FN expression abrogated the pro‑adhesive and pro‑survival effects of Dex in melanoma cells. Extracellular FN significantly enhanced melanoma cell adhesion and survival in the presence of cisplatin, whereas partially blocking extracellular FN signaling with a CD44 antibody significantly reduced FN‑enhanced adhesion and survival. This indicated that the upregulation of FN contributed to the pro‑survival effect of Dex by enhancing cell adhesion. It was also observed that activation of the PI3K/AKT signaling pathway by extracellular FN was involved in the FN‑mediated increase in melanoma cell survival. These findings increase understanding of the possible mechanisms by which GCs regulate melanoma cell adhesion and survival.

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