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

Content Provider	Springer Nature Link
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.
Copyright Year	2013
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.
Starting Page	199
Ending Page	211
Page Count	13
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	31
Issue Number	2
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-10-26
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Prostate cancer Metastasis Non-canonical Wnt pathway PITX2 Bone Cancer Research Biomedicine general Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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