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2015 ; 6
(24
): 20636-49
Nephropedia Template TP
gab.com Text
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English Wikipedia
Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor
suppressor in human melanoma cells
#MMPMID26010068
Wang J
; Ding N
; Li Y
; Cheng H
; Wang D
; Yang Q
; Deng Y
; Yang Y
; Li Y
; Ruan X
; Xie F
; Zhao H
; Fang X
Oncotarget
2015[Aug]; 6
(24
): 20636-49
PMID26010068
show ga
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 HIF1? 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.
|Animals
[MESH]
|Cell Line, Tumor
[MESH]
|Cell Proliferation/drug effects
[MESH]
|Female
[MESH]
|Gene Knockdown Techniques
[MESH]
|Genes, Tumor Suppressor
[MESH]
|Humans
[MESH]
|Insulin-Like Growth Factor Binding Protein 5/*metabolism
[MESH]
|Kruppel-Like Factor 4
[MESH]
|Melanoma/*metabolism/pathology
[MESH]
|Mice
[MESH]
|Mice, SCID
[MESH]
|Mitogen-Activated Protein Kinase 3/metabolism
[MESH]
free
free
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