NDLI: The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression

Content Provider	Springer Nature Link
Author	Vincan, Elizabeth Barker, Nick
Copyright Year	2008
Abstract	The constitutive activation of β-catenin-dependent (‘canonical’) Wnt signalling is a necessary initiating event in the genesis of most colorectal cancers. As this constitutive activation occurs through genetic mutation of one of the down-stream components of the signalling pathway, it was presumed that additional regulation of β-catenin-dependent Wnt signalling would be inconsequential. However, it is now recognised that additional modulation of β-catenin-dependent Wnt signalling is involved in tumour progression, and many of the genes associated with tumour invasion and metastasis are β-catenin/TCF transcriptional target genes that are dynamically regulated during cancer progression. Intriguingly, the demonstration that naturally occurring inhibitors of Wnt-Frizzled (FZD) interaction are bona fide tumour suppressors in this cancer suggests that additional modulation of Wnt signalling is via the upstream components of the pathway. This is corroborated by recent studies that demonstrate tumour-promoting roles for Wnt and FZD per se. Moreover, both β-catenin-dependent and β-catenin-independent Wnt/FZD-mediated signalling is implicated during the dynamic and reversible EMT and MET that underscore colorectal cancer progression. Importantly, therapeutic targeting of the Wnt signalling pathway at the plasma membrane is clearly indicated by the profound anti-tumour activity of small molecule inhibitors and dominant-negative receptor constructs that target the receptor complex. The potential to effectively target EMT and MET processes at the plasma membrane via the upstream components of the Wnt signalling pathway offers new hope for anti-cancer therapy.
Starting Page	657
Ending Page	663
Page Count	7
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	25
Issue Number	6
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2008-03-19
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	β-Catenin Colorectal cancer EMT Frizzled MET Tumour invasion and metastasis Vertebrate non-canonical Wnt pathways Wnt signalling Surgical Oncology Hematology Oncology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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