PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer

Vela, I., Morrissey, C., Zhang, X., Chen, S., Corey, E., Strutton, G. M., Nelson, C. C., Nicol, D. L., Clements, J. A. and Gardiner, E. M. (2013) PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer. Clinical and Experimental Metastasis, 31 2: 199-211. doi:10.1007/s10585-013-9620-7


Author Vela, I.
Morrissey, C.
Zhang, X.
Chen, S.
Corey, E.
Strutton, G. M.
Nelson, C. C.
Nicol, D. L.
Clements, J. A.
Gardiner, E. M.
Title PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer
Journal name Clinical and Experimental Metastasis   Check publisher's open access policy
ISSN 0262-0898
1573-7276
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s10585-013-9620-7
Open Access Status DOI
Volume 31
Issue 2
Start page 199
End page 211
Total pages 13
Place of publication Dordrecht, The Netherlands
Publisher Springer Netherlands
Collection year 2014
Language eng
Subject 2730 Oncology
1306 Cancer Research
Abstract The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.
Keyword Bone
Metastasis
Non-canonical Wnt pathway
Prostate cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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