title: Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor suppressor in human melanoma cells.
abstract: The insulin-like growth factor binding protein 5 (IGFBP5), which is often dysregulated in human cancers, plays a crucial role in carcinogenesis and cancer development. However, the function and underlying mechanism of IGFBP5 in tumor growth and metastasis has been elusive, particularly in malignant human melanoma. Here, we reported that IGFBP5 acts as an important tumor suppressor in melanoma tumorigenicity and metastasis by a series of experiments including transwell assay, xenograft model, in vivo tumor metastasis experiment, and RNA-Seq. Overexpression of IGFBP5 in A375, a typical human melanoma cell line, inhibited cell malignant behaviors significantly, including in vitro proliferation, anchorage-independent growth, migration and invasion, as well as in vivo tumor growth and pulmonary metastasis. In addition, overexpression of IGFBP5 suppressed epithelial-mesenchymal transition (EMT), and decreased the expression of E-cadherin and the key stem cell markers NANOG, SOX2, OCT4, KLF4, and CD133. Furthermore, IGFBP5 exerts its inhibitory activities by reducing the phosphorylation of IGF1R, ERK1/2, and p38-MAPK kinases and abating the expression of HIF1α and its target genes, VEGF and MMP9. All these findings were confirmed by IGFBP5 knockdown in human melanoma cell line A2058. Taken together, these results shed light on the mechanism of IGFBP5 as a potential tumor-suppressor in melanoma progression, indicating that IGFBP5 might be a novel therapeutic target for human melanoma.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Junyun
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Biology, Hebei Academy of Sciences, Shijiazhuang, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Youhui
authors.initials: Y
authors.lastname: Deng
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yaran
authors.initials: Y
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Ruan
authors.affiliation: Department of Dermatology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Dermatology, General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D014162:Transfection
chemical_list: D018975:Insulin-Like Growth Factor Binding Protein 5; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D048052:Mitogen-Activated Protein Kinase 3
keywords: EMT; ERK-MAPK; IGFBP5; malignant melanoma; tumor suppressor