title: GnRH participates in the self-renewal of A549-derived lung cancer stem-like cells through upregulation of the JNK signaling pathway.
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.
authors.affiliation: Department of Oncology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Oncology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Huang
authors.affiliation: Cancer Research Institute of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Hongda
authors.initials: H
authors.lastname: Lu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D007987:Gonadotropin-Releasing Hormone