Evidence map›Paper›PMID 28966723›Full record

ArticleGenes & cancer2017

Extracellular LDLR repeats modulate Wnt signaling activity by promoting LRP6 receptor endocytosis mediated by the Itch E3 ubiquitin ligase.

Sapna Vijayakumar, Guizhong Liu, Huei-Chi Wen, Yaa Abu, Robert Chong, Horacio Nastri, Gadi G Bornstein, Zhen-Qiang Pan, Stuart A Aaronson

Open access · diamondAbstract read
In one paragraph

Article in Genes & cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 2 countries.

Sapna VijayakumarOncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Guizhong LiuOncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Huei-Chi WenOncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Yaa AbuPrinceton University, Princeton, New Jersey, USA.
Robert ChongOncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Horacio NastriCenters for Therapeutic Innovation, Pfizer Inc. New York, NY, USA.
Gadi G BornsteinCenters for Therapeutic Innovation, Pfizer Inc. New York, NY, USA.
Zhen-Qiang PanOncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Stuart A AaronsonOncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn School of Medicine at Mount Sinai · USARTS Group (China) · CNIncyte (United States) · USPfizer (United States) · USPrinceton University · USTesaro (United States) · US

Funding

Regulation of Wnt Pathway SpecificityR01HD066319 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AARONSON, STUART A, MLODZIK, MAREK · 2012 to 2016
$2.0M
Defining mechanisms and targets in Wnt addicted human malignancies (PQ22)R01CA170702 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AARONSON, STUART A · 2012 to 2015
$1.4M
NCI NIH HHS R01 CA170702NICHD NIH HHS R01 HD066319
6 · The paper itself

Abstract

The LOW-density lipoprotein related protein 6 (LRP6) receptor is an important effector of canonical Wnt signaling, a developmental pathway, whose dysregulation has been implicated in various diseases including cancer. The membrane proximal low-density lipoprotein (LDL) receptor repeats in LRP6 exhibit homology to ligand binding repeats in the LDL receptor (LDLR), but lack known function. We generated single amino acid substitutions of LRP6-LDLR repeat residues, which are highly conserved in the human LDLR and mutated in patients with Familial Hypercholesteremia (FH). These substitutions negatively impacted LRP6 internalization and activation of Wnt signaling. By mass spectrometry, we observed that the Itch E3 ubiquitin ligase associated with and ubiquitinated wild type LRP6 but not the LDLR repeat mutants. These findings establish the involvement of LRP6-LDLR repeats in the regulation of canonical Wnt signaling.

Indexed as

internalizationItch E3 ubiquitin ligaseLDLRRLRP6sarcomaWnt

Identifiers

PMID28966723
PMCPMC5620007
OpenAlexW3024470649

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.