GnRH participates in the self-renewal of A549-derived lung cancer stem-like cells through upregulation of the JNK signaling pathway

Lu,Chi; Huang,Ting; Chen,Weiqun; Lu,Hongda

doi:10.3892/or.2015.3956

GnRH participates in the self-renewal of A549-derived lung cancer stem-like cells through upregulation of the JNK signaling pathway

Authors:
- Chi Lu
- Ting Huang
- Weiqun Chen
- Hongda Lu
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Affiliations: Department of Oncology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China, Cancer Research Institute of Wuhan, Wuhan, Hubei 430014, P.R. China
Published online on: May 6, 2015 https://doi.org/10.3892/or.2015.3956
Pages: 244-250

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Abstract

Lung cancer is the leading cause of cancer-related mortality in humans. Exploration of the mechanisms underlying the self-renewal and stemness maintenance of cancer stem-like cells (CSLCs) will open new avenues in lung cancer diagnosis and therapy. Here, we isolated and identified a subpopulation of lung cancer stem-like cells (LCSLCs) from non-small cell lung carcinoma (NSCLC) A549 cells with features including self-renewal capacity in vitro, elevated tumorigenic activity in vivo, and high expression of stemness markers CD44, CD133, aldehyde dehydrogenase 1 (ALDH1) and Sox2, using a serum-free suspension sphere-forming culture method. We then found a higher expression level of gonadotropin‑releasing hormone (GnRH) in the LCSLCs using a microarray assay, suggesting that GnRH may play a role in the self‑renewal capacity and stemness maintenance in lung cancer cells. In addition, the suppression of GnRH capacity negatively regulated self-renewal and stemness maintenance in the LCSLCs. Overexpression of GnRH promoted stemness properties of A549-derived LCSLCs, indicating that GnRH expression is essential for the self-renewal and stemness maintenance in LCSLCs. Moreover, further investigations demonstrated that the promotion of GnRH functions of self‑renewal and stemness maintenance in LCSLCs was associated with the JNK signaling pathway. Therefore, our results showed that GnRH participates in the self-renewal capacity and stemness maintenance of LCSLCs by upregulating the JNK signaling pathway, and GnRH may be useful as an alternative LCSLC therapy.

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