title: Transcriptional activation of NANOG by YBX1 promotes lung cancer stem-like properties and metastasis.
abstract: Aberrant overexpression of the transcription/translation factor Y-box-binding protein-1 (YBX1) is associated with non-small cell lung cancer (NSCLC) aggressiveness. Cancer stem cells (CSCs) contribute to the tumorigenesis and metastasis of NSCLC. Hitherto, the mechanism by which YBX1 regulates CSCs and metastasis in NSCLC remains unclear. Here, we demonstrated that YBX1 levels were elevated in NSCLC tissues and cell lines. Enforced expression of YBX1 promoted NSCLC cells invasion, sphere forming ability and ALDH1+population. Conversely, reduced YBX1 impaired CSC properties of NSCLC cells in vitro and tumor-initiating frequencies, as well as metastasis in vivo. Importantly, we described a mechanism whereby YBX1 directly promoted NANOG, a transcription factor, transcriptional activation. Depletion of NANOG abolished the enhanced ability of invasion and sphere formation in YBX1 elevated-A549 cells. Collectively, these findings demonstrate a novel role of YBX1 in maintaining the stemness of CSCs and metastasis, unveiling YBX1 as promising therapeutic target for NSCLC treatments.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: College of Stomatology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.affiliation: Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Zhuoshi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Jianglong
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, 250000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Shilei
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Fengzhou
authors.initials: F
authors.lastname: Li
authors.affiliation: Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China. Electronic address: lijinxiu@dmu.edu.cn.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China. Electronic address: guchundong@dmu.edu.cn.
authors.forename: Chundong
authors.initials: C
authors.lastname: Gu
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D000071317:Nanog Homeobox Protein / Q000235:genetics*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D051840:Y-Box-Binding Protein 1 / Q000235:genetics*
chemical_list: C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human
keywords: Cancer stem cell; Lung cancer; Metastasis; NANOG; YBX1