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Dual mechanisms of action of the RNA-binding protein human antigen R explains its regulatory effect on melanoma cell migration.

Moradi, Farnaz LU ; Berglund, Pontus LU ; Linnskog, Rickard LU ; Leandersson, Karin LU ; Andersson, Tommy LU and Prasad, Chandra LU (2016) In Translational Research 172. p.45-60
Abstract
Overexpression of wingless-type MMTV integration site family 5A (WNT5A) plays a significant role in melanoma cancer progression; however, the mechanism(s) involved remains unknown. In breast cancer, the human antigen R (HuR) has been implicated in the regulation of WNT5A expression. Here, we demonstrate that endogenous expression of WNT5A correlates with levels of active HuR in HTB63 and WM852 melanoma cells and that HuR binds to WNT5A messenger RNA in both cell lines. Although the HuR inhibitor MS-444 significantly impaired migration in both melanoma cell lines, it reduced WNT5A expression only in HTB63 cells, as did small interfering RNA knockdown of HuR. Consistent with this finding, MS-444-induced inhibition of HTB63 cell migration was... (More)
Overexpression of wingless-type MMTV integration site family 5A (WNT5A) plays a significant role in melanoma cancer progression; however, the mechanism(s) involved remains unknown. In breast cancer, the human antigen R (HuR) has been implicated in the regulation of WNT5A expression. Here, we demonstrate that endogenous expression of WNT5A correlates with levels of active HuR in HTB63 and WM852 melanoma cells and that HuR binds to WNT5A messenger RNA in both cell lines. Although the HuR inhibitor MS-444 significantly impaired migration in both melanoma cell lines, it reduced WNT5A expression only in HTB63 cells, as did small interfering RNA knockdown of HuR. Consistent with this finding, MS-444-induced inhibition of HTB63 cell migration was restored by the addition of recombinant WNT5A, whereas MS-444-induced inhibition of WM852 cell migration was restored by the addition of recombinant matrix metalloproteinase-9, another HuR-regulated protein. Clearly, HuR positively regulates melanoma cell migration via at least 2 distinct mechanisms making HuR an attractive therapeutic target for halting melanoma dissemination. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Translational Research
volume
172
pages
45 - 60
publisher
Elsevier
external identifiers
  • pmid:26970271
  • scopus:84962560134
  • wos:000376471400005
ISSN
1878-1810
DOI
10.1016/j.trsl.2016.02.007
language
English
LU publication?
yes
id
5ae6b1a8-d91f-41c3-9d32-61a8d7014854 (old id 8852518)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26970271?dopt=Abstract
date added to LUP
2016-03-15 15:11:17
date last changed
2017-01-01 07:39:14
@article{5ae6b1a8-d91f-41c3-9d32-61a8d7014854,
  abstract     = {Overexpression of wingless-type MMTV integration site family 5A (WNT5A) plays a significant role in melanoma cancer progression; however, the mechanism(s) involved remains unknown. In breast cancer, the human antigen R (HuR) has been implicated in the regulation of WNT5A expression. Here, we demonstrate that endogenous expression of WNT5A correlates with levels of active HuR in HTB63 and WM852 melanoma cells and that HuR binds to WNT5A messenger RNA in both cell lines. Although the HuR inhibitor MS-444 significantly impaired migration in both melanoma cell lines, it reduced WNT5A expression only in HTB63 cells, as did small interfering RNA knockdown of HuR. Consistent with this finding, MS-444-induced inhibition of HTB63 cell migration was restored by the addition of recombinant WNT5A, whereas MS-444-induced inhibition of WM852 cell migration was restored by the addition of recombinant matrix metalloproteinase-9, another HuR-regulated protein. Clearly, HuR positively regulates melanoma cell migration via at least 2 distinct mechanisms making HuR an attractive therapeutic target for halting melanoma dissemination.},
  author       = {Moradi, Farnaz and Berglund, Pontus and Linnskog, Rickard and Leandersson, Karin and Andersson, Tommy and Prasad, Chandra},
  issn         = {1878-1810},
  language     = {eng},
  pages        = {45--60},
  publisher    = {Elsevier},
  series       = {Translational Research},
  title        = {Dual mechanisms of action of the RNA-binding protein human antigen R explains its regulatory effect on melanoma cell migration.},
  url          = {http://dx.doi.org/10.1016/j.trsl.2016.02.007},
  volume       = {172},
  year         = {2016},
}