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A Role for the WNT Co-Receptor LRP6 in Pathogenesis and Therapy of Epithelial Cancers

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada
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Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1162; https://doi.org/10.3390/cancers11081162
Received: 1 July 2019 / Revised: 8 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
(This article belongs to the Special Issue Targeting Wnt Signaling in Cancer)
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Abstract

The WNT/β-catenin signaling pathway controls stem and progenitor cell proliferation, survival and differentiation in epithelial tissues. Aberrant stimulation of this pathway is therefore frequently observed in cancers from epithelial origin. For instance, colorectal and hepatic cancers display activating mutations in the CTNNB1 gene encoding β-catenin, or inactivating APC and AXIN gene mutations. However, these mutations are uncommon in breast and pancreatic cancers despite nuclear β-catenin localization, indicative of pathway activation. Notably, the low-density lipoprotein receptor-related protein 6 (LRP6), an indispensable co-receptor for WNT, is frequently overexpressed in colorectal, liver, breast and pancreatic adenocarcinomas in association with increased WNT/β -catenin signaling. Moreover, LRP6 is hyperphosphorylated in KRAS-mutated cells and in patient-derived colorectal tumours. Polymorphisms in the LRP6 gene are also associated with different susceptibility to developing specific types of lung, bladder and colorectal cancers. Additionally, recent observations suggest that LRP6 dysfunction may be involved in carcinogenesis. Indeed, reducing LRP6 expression and/or activity inhibits cancer cell proliferation and delays tumour growth in vivo. This review summarizes current knowledge regarding the biological function and regulation of LRP6 in the development of epithelial cancers—especially colorectal, liver, breast and pancreatic cancers. View Full-Text
Keywords: low-density lipoprotein receptor-related protein 6; LRP6; carcinoma; WNT signaling; β-catenin low-density lipoprotein receptor-related protein 6; LRP6; carcinoma; WNT signaling; β-catenin
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Raisch, J.; Côté-Biron, A.; Rivard, N. A Role for the WNT Co-Receptor LRP6 in Pathogenesis and Therapy of Epithelial Cancers. Cancers 2019, 11, 1162.

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