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The WNT5A Agonist Foxy5 Reduces the Number of Colonic Cancer Stem Cells in a Xenograft Mouse Model of Human Colonic Cancer

Osman, Janina LU ; Bellamkonda, Kishan LU ; Liu, Qing LU ; Andersson, Tommy LU and Sjölander, Anita LU (2019) In Anticancer research 39(4). p.1719-1728
Abstract

BACKGROUND: The wingless-type mammary tumour virus integration site 5A (WNT5A) agonist Foxy5 was shown in vitro to affect intracellular signalling implicated in the regulation of colonic cancer stem cells (CSCs). MATERIALS AND METHODS: In order to study whether Foxy5 can modulate CSCs, either HT-29 or Caco-2 human colonic cancer cells, both lacking endogenous WNT5A expression, were inoculated subcutaneously into nude mice. RESULTS: Foxy5 reduced the expression of the stem-cell marker aldehyde dehydrogenase and, interestingly, the specific colon CSC marker double cortin-like kinase 1. Foxy5 also reduced active β-catenin and the expression of its downstream target Achaete Scute complex homolog 2, a CSC-preserving transcription factor.... (More)

BACKGROUND: The wingless-type mammary tumour virus integration site 5A (WNT5A) agonist Foxy5 was shown in vitro to affect intracellular signalling implicated in the regulation of colonic cancer stem cells (CSCs). MATERIALS AND METHODS: In order to study whether Foxy5 can modulate CSCs, either HT-29 or Caco-2 human colonic cancer cells, both lacking endogenous WNT5A expression, were inoculated subcutaneously into nude mice. RESULTS: Foxy5 reduced the expression of the stem-cell marker aldehyde dehydrogenase and, interestingly, the specific colon CSC marker double cortin-like kinase 1. Foxy5 also reduced active β-catenin and the expression of its downstream target Achaete Scute complex homolog 2, a CSC-preserving transcription factor. Foxy5 also reduced cyclo-oxygenase 2 expression, responsible for the formation of the CSC-promoting prostaglandin E2 (PGE2), but increased that of 15-hydroxyprostaglandin dehydrogenase expression, a PGE2-degrading enzyme. Accordingly, Foxy5 impairs both β-catenin and PGE2 signalling, both of which have been implicated in promoting the niche of colonic CSCs. CONCLUSION: Our data suggest that Foxy5 can complement the traditional adjuvant chemotherapeutic treatment to which CSCs are resistant.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cancer stem cells, Foxy5 peptide, tumour cell signalling, WNT5A
in
Anticancer research
volume
39
issue
4
pages
10 pages
publisher
International Institute of Cancer Research
external identifiers
  • scopus:85064476731
ISSN
1791-7530
DOI
10.21873/anticanres.13278
language
English
LU publication?
yes
id
03f648b3-37fe-4410-a717-45178efc99c1
date added to LUP
2019-05-03 12:42:17
date last changed
2019-10-15 07:02:45
@article{03f648b3-37fe-4410-a717-45178efc99c1,
  abstract     = {<p>BACKGROUND: The wingless-type mammary tumour virus integration site 5A (WNT5A) agonist Foxy5 was shown in vitro to affect intracellular signalling implicated in the regulation of colonic cancer stem cells (CSCs). MATERIALS AND METHODS: In order to study whether Foxy5 can modulate CSCs, either HT-29 or Caco-2 human colonic cancer cells, both lacking endogenous WNT5A expression, were inoculated subcutaneously into nude mice. RESULTS: Foxy5 reduced the expression of the stem-cell marker aldehyde dehydrogenase and, interestingly, the specific colon CSC marker double cortin-like kinase 1. Foxy5 also reduced active β-catenin and the expression of its downstream target Achaete Scute complex homolog 2, a CSC-preserving transcription factor. Foxy5 also reduced cyclo-oxygenase 2 expression, responsible for the formation of the CSC-promoting prostaglandin E2 (PGE2), but increased that of 15-hydroxyprostaglandin dehydrogenase expression, a PGE2-degrading enzyme. Accordingly, Foxy5 impairs both β-catenin and PGE2 signalling, both of which have been implicated in promoting the niche of colonic CSCs. CONCLUSION: Our data suggest that Foxy5 can complement the traditional adjuvant chemotherapeutic treatment to which CSCs are resistant.</p>},
  author       = {Osman, Janina and Bellamkonda, Kishan and Liu, Qing and Andersson, Tommy and Sjölander, Anita},
  issn         = {1791-7530},
  keyword      = {cancer stem cells,Foxy5 peptide,tumour cell signalling,WNT5A},
  language     = {eng},
  number       = {4},
  pages        = {1719--1728},
  publisher    = {International Institute of Cancer Research},
  series       = {Anticancer research},
  title        = {The WNT5A Agonist Foxy5 Reduces the Number of Colonic Cancer Stem Cells in a Xenograft Mouse Model of Human Colonic Cancer},
  url          = {http://dx.doi.org/10.21873/anticanres.13278},
  volume       = {39},
  year         = {2019},
}