misspliced mutants of LRP5 support enhanced beta-catenin-dependent signaling

Stable Identifier
R-HSA-5339711
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Frequent expression of an internally deleted LRP5 has been identified in parathyroid and breast cancers. Expression of the internally deleted LRP5 protein results in elevated levels of the active, unphosphorylated beta-catenin, enhanced expression of the both WNT-dependent reporter genes and the endogenous WNT-target gene MYC, and is required for cellular proliferation (Bjorklund et al, 2007a, b; Bjorklund et al, 2009). The in-frame internal deletion, which removes residues 666-809, arises through the aberrant use of cryptic splice sites in imperfect direct repeat sequences in exons 9 and 11 (Bjorklund et al, 2007b). This region has been shown to contain residues required for inhibition of beta-catenin activity by the negative regulator DKK1; consistent with this, expression of LRP5del666-809 is insensitive to inhibition by DKK1 (Zhang et al, 2004; Bjorklund et al, 2007b; Bjorklund et al, 2009). It has not been determined whether the LRP666-809del affects the interaction with SOST.

Literature References
PubMed ID Title Journal Year
18044981 An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/beta-catenin signaling

Björklund, P, Akerström, G, Westin, G

PLoS Med. 2007
19158955 The internally truncated LRP5 receptor presents a therapeutic target in breast cancer

Björklund, P, Svedlund, J, Olsson, AK, Akerström, G, Westin, G

PLoS ONE 2009
17047023 Accumulation of nonphosphorylated beta-catenin and c-myc in primary and uremic secondary hyperparathyroid tumors

Björklund, P, Akerström, G, Westin, G

J. Clin. Endocrinol. Metab. 2007
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
parathyroid carcinoma 1540 malignant neoplasm of parathyroid gland, malignant neoplasm of the Parathyroid, parathyroid gland cancer, neoplasm of parathyroid gland, carcinoma of Parathyroid gland, Parathyroid gland neoplasm, malignant tumor of parathyroid gland (disorder), parathyroid neoplasm
cancer 162 malignant tumor, malignant neoplasm, primary cancer
breast cancer 1612 malignant tumor of the breast, mammary cancer, malignant neoplasm of breast, mammary tumor, primary breast cancer, breast cancer, Ca breast - NOS, breast tumor
Authored
Reviewed
Created
Cite Us!