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WNT5A-mediated β-catenin-independent signalling is a novel regulator of cancer cell metabolism.

Sherwood, Victoria LU ; Chaurasiya, Shivendra LU ; Ekström, Elin LU ; Guilmain, William LU ; Liu, Qing LU ; Koeck, Tomas; Brown, Kate; Hansson, Karin M LU ; Agnarsdóttir, Margrét and Bergqvist, Michael, et al. (2014) In Carcinogenesis 35(4). p.784-794
Abstract
WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligand's role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of β-catenin-independent WNT signalling in oncology. Here, we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong... (More)
WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligand's role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of β-catenin-independent WNT signalling in oncology. Here, we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong correlation (P < 0.001) between the expression of WNT5A and LDH isoform V in a cohort of melanocytic neoplasms. We also found effects of WNT5A on energy metabolism in breast cancer cells, but rather than promoting aerobic glycolysis as it does in melanoma, WNT5A signalling increased oxidative phosphorylation rates in breast cancer cells. These findings support a new role for WNT5A in the metabolic reprogramming of cancer cells that is a context- dependent event. (Less)
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Contribution to journal
publication status
published
subject
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Carcinogenesis
volume
35
issue
4
pages
784 - 794
publisher
Oxford University Press
external identifiers
  • pmid:24293407
  • wos:000335001800006
  • scopus:84898645562
ISSN
0143-3334
DOI
10.1093/carcin/bgt390
project
CREATE Health
language
English
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yes
id
43a027f6-e32e-4739-9ede-0914c6127b46 (old id 4225414)
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http://www.ncbi.nlm.nih.gov/pubmed/24293407?dopt=Abstract
date added to LUP
2014-01-02 21:27:13
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2017-08-13 03:07:14
@article{43a027f6-e32e-4739-9ede-0914c6127b46,
  abstract     = {WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligand's role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of β-catenin-independent WNT signalling in oncology. Here, we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong correlation (P &lt; 0.001) between the expression of WNT5A and LDH isoform V in a cohort of melanocytic neoplasms. We also found effects of WNT5A on energy metabolism in breast cancer cells, but rather than promoting aerobic glycolysis as it does in melanoma, WNT5A signalling increased oxidative phosphorylation rates in breast cancer cells. These findings support a new role for WNT5A in the metabolic reprogramming of cancer cells that is a context- dependent event.},
  author       = {Sherwood, Victoria and Chaurasiya, Shivendra and Ekström, Elin and Guilmain, William and Liu, Qing and Koeck, Tomas and Brown, Kate and Hansson, Karin M and Agnarsdóttir, Margrét and Bergqvist, Michael and Jirström, Karin and Ponten, Fredrik and James, Peter and Andersson, Tommy},
  issn         = {0143-3334},
  language     = {eng},
  number       = {4},
  pages        = {784--794},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {WNT5A-mediated β-catenin-independent signalling is a novel regulator of cancer cell metabolism.},
  url          = {http://dx.doi.org/10.1093/carcin/bgt390},
  volume       = {35},
  year         = {2014},
}