ArticleDevelopmental cell2018
APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway.
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Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60citing papers in PubMed
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60 citing papers in PubMed, 102 citations in OpenAlex.
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- Human papillomavirus16 E7 enhances cell stemness by regulating the APC2/SPIN4/β-catenin axis in cervical cancer.Oncogenesis · 2026Article
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- Cholesterol-targeting Wnt-β-catenin signaling inhibitors for colorectal cancer.Nature chemical biology · 2025Article
- The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- A truncation mutant of adenomatous polyposis coli impairs apical cell extrusion through elevated epithelial tissue tension.Cytoskeleton (Hoboken, N.J.) · 2025Article
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- Molecular functions of microRNAs in colorectal cancer: recent roles in proliferation, angiogenesis, apoptosis, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
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- APC and ZBTB2 May Mediate M2 Macrophage Infiltration to Promote the Development of Renal Fibrosis: A Bioinformatics Analysis.BioMed research international · 2024Article
- The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.Nature communications · 2023Article
- The WNT/β-catenin system in chronic kidney disease-mineral bone disorder syndrome.International urology and nephrology · 2023Review
- Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin.Nature communications · 2023Article
- SELENOP modifies sporadic colorectal carcinogenesis and WNT signaling activity through LRP5/6 interactions.The Journal of clinical investigation · 2023Article
- The Relationship between LRP6 and Wnt/β-Catenin Pathway in Colorectal and Esophageal Cancer.Life (Basel, Switzerland) · 2023Article
- β-catenin-dependent High Bone Mass Induced by Loss of APC in Osteoblasts Does Not Require Lrp5 or Lrp6.microPublication biology · 2023Article
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Authors and funding
18 authors at 6 institutions in 1 country.
Kenyi Saito-DiazDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Hassina BenchabaneDepartment of Molecular and Systems Biology and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA.
Ajit TiwariDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
Ai TianDepartment of Molecular and Systems Biology and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA.
Bin LiMolecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Joshua J ThompsonDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Annastasia S HydeDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Leah M SawyerDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Jeanne N JodoinDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Eduardo SantosDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Laura A LeeDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Robert J CoffeyDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
R Daniel BeauchampDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Christopher S WilliamsDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Anne K KenworthyDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
David J RobbinsMolecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Yashi AhmedDepartment of Molecular and Systems Biology and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA. Electronic address: yashi.ahmed@dartmouth.edu.
Ethan LeeDepartment of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: ethan.lee@vanderbilt.edu.
Vanderbilt University · USDartmouth College · USVanderbilt University Medical Center · USMassachusetts Institute of Technology · USSylvester Comprehensive Cancer Center · USUniversity of Miami · US
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8MVanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MUnderstanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3MResource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5MIntegrated approach to study early and late events in colonic neoplasia: mouse to manR35CA197570 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Robert J. Coffey · 2017 to 2026
$9.4MMechanism of Wnt signal transductionR35GM122516 · NIGMS · VANDERBILT UNIVERSITY · PI ETHAN LEE · 2017 to 2026
$5.8MREGULATION OF GUT EPITHELIAL CELL PROLIFERATIONR01CA069457 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BEAUCHAMP, ROBERT DANIEL · 1995 to 2016
$4.4MFunction and assembly of toxin-stabilized domainsR01GM106720 · NIGMS · VANDERBILT UNIVERSITY · PI KENWORTHY, ANNE K · 2013 to 2020
$2.7MAPC Tumor Suppressor in Cell Differentiation and DeathR01CA105038 · NCI · DARTMOUTH COLLEGE · PI AHMED, YASMATH · 2005 to 2016
$2.6MBLRD VA I01 BX001426NCATS NIH HHS UL1 TR000445NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA095103NCI NIH HHS R01 CA069457NCI NIH HHS R01 CA105038NCI NIH HHS R35 CA197570NIDDK NIH HHS F30 DK111107NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK099204NIGMS NIH HHS R01 GM081635NIGMS NIH HHS R01 GM103926NIGMS NIH HHS R01 GM106720NIGMS NIH HHS R01 GM121421NIGMS NIH HHS R01 GM122222NIGMS NIH HHS R35 GM122516NIGMS NIH HHS T32 GM007347NIH HHS P40 OD018537
Abstract
Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation. We show that APC exists in a complex with clathrin and that Wnt pathway activation in APC-deficient cells requires clathrin-mediated endocytosis. Finally, we demonstrate conservation of this mechanism in Drosophila intestinal stem cells. We propose a model in which APC and APC2 function to promote β-catenin degradation, and APC also acts as a molecular "gatekeeper" to block receptor activation via the clathrin pathway.
Indexed as
Adenomatous Polyposis Coli ProteinAnimalsbeta CateninCells, CulturedClathrinDrosophila melanogasterEndocytosisFemaleHumansInfantLigandsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedAdenomatous Polyposis Coli Proteinbeta CateninClathrinLigandsWnt ProteinsAPCcaveolinclathrincolorectal cancerendocytosisLRP6Wnt signalingβ-catenin
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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.