Affinage

IQGAP3

Ras GTPase-activating-like protein IQGAP3 · UniProt Q86VI3

Length
1631 aa
Mass
184.7 kDa
Annotated
2026-06-10
51 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IQGAP3 is a multivalent scaffolding protein that couples Rho-family and Ras GTPase activation to actin cytoskeletal organization, cell proliferation, and migration (PMID:17244649, PMID:18604197, PMID:32824461). It acts as a direct effector of active Rac1 and Cdc42, binds actin filaments, and is required for GTPase-driven cytoskeletal outgrowth in neurons (PMID:17244649); it also binds the GTP-bound form of Ras and drives proliferation through Ras-dependent ERK activation, an axis that operates downstream of FGFR1/Ras signaling and within the EGFR-ERK pathway (PMID:18604197, PMID:26286209, PMID:24849319). Through its IQ motifs IQGAP3 engages calmodulin in a calcium-dependent manner (PMID:21299499). Functionally it localizes to the leading edge of migrating cells and to the cleavage furrow and midbody during cytokinesis, where its proper positioning is required for cleavage furrow ingression (PMID:29522098, PMID:32824461), and it lowers cell-cell adhesion via E-cadherin/β-catenin interactions (PMID:32824461). IQGAP3 nucleates contractility through a PAK6-IQGAP3-RhoA pathway controlling actomyosin tension, invadopodia, and migration (PMID:38763182), an activity antagonized by IFFO1, which competitively blocks the IQGAP3-Cdc42 interaction (PMID:40634295). Beyond cytoskeletal control, IQGAP3 scaffolds diverse signaling nodes: it activates TGF-β/Smad signaling to drive EMT (PMID:28810875, PMID:40945199), promotes β-catenin accumulation by disrupting the Axin1-CK1α interaction in a Wnt feedback loop (PMID:40830657), couples to the ATM/ATR DNA damage response via Rad17 and the MRN complex (PMID:32896617), and modulates cell-cycle progression through the MMS19/XPD/CAK axis (PMID:34183451). It also binds and stabilizes the stem-cell factor SOX2 to sustain self-renewal and radioresistance (PMID:42251046), and serves as a marker and proliferation regulator of gastric isthmus stem cells through the Ras pathway (PMID:33293280). IQGAP3 expression is controlled transcriptionally by YAP/TEAD, E2F1, FOXD2, MYB, and KLF2 (PMID:34183451, PMID:42251046, PMID:30906629, PMID:37724892, PMID:40772604, PMID:41317937) and post-transcriptionally by m6A-dependent stabilization via IGF2BP1/IGF2BP2 with METTL3/WTAP (PMID:36217548, PMID:40945199, PMID:41317937), while its protein levels are limited by PRKN-mediated ubiquitination (PMID:39343867).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 High

    Established IQGAP3 as a direct GTPase effector by showing it binds active Rac1/Cdc42, associates with actin, and is required for GTPase-driven cytoskeletal outgrowth.

    Evidence GTPase effector pulldowns, actin co-sedimentation, immunofluorescence, and siRNA neurite-outgrowth assays in neurons and PC12 cells

    PMID:17244649

    Open questions at the time
    • Did not define the structural basis of GTPase binding
    • Restricted to neuronal cytoskeletal phenotypes
  2. 2008 High

    Placed IQGAP3 in a proliferation pathway by showing it binds GTP-bound Ras and drives ERK-dependent cell-cycle re-entry.

    Evidence Co-IP with active Ras, MEK-inhibitor (U0126) epistasis, gain/loss-of-function proliferation and ERK activity assays

    PMID:18604197

    Open questions at the time
    • Whether IQGAP3 acts upstream or as a scaffold for Ras was not biochemically resolved
    • No structural mapping of the Ras-binding interface
  3. 2011 Medium

    Characterized the IQ-motif interactome, defining calcium-dependent calmodulin binding across all four IQ motifs.

    Evidence Synthetic peptide binding with native gel electrophoresis and modelling

    PMID:21299499

    Open questions at the time
    • Peptide-based rather than full-length protein
    • Functional consequence of CaM binding untested in cells
  4. 2015 High

    Connected IQGAP3 to Ras-MAPK-dependent tumorigenesis in vivo, establishing IQGAP scaffolding as tumor-selective.

    Evidence Engineered human skin tissue, knockdown, and dominant-negative IQGAP IQ-motif decoys with MAPK readouts; zebrafish morpholino knockdown with dominant-negative FGFR1/Ras mRNA rescue

    PMID:25848980 PMID:26286209

    Open questions at the time
    • Skin decoys targeted IQGAP1 primarily; IQGAP3-specific contribution inferred from knockdown
    • FGFR1-Ras epistasis is genetic, not biochemical
  5. 2018 Medium

    Tied IQGAP3 localization to cytokinesis, showing midbody/stembody positioning is required for cleavage furrow ingression.

    Evidence Live imaging and immunofluorescence in cardiomyocytes with quantitative localization analysis

    PMID:29522098

    Open questions at the time
    • Mechanism linking astral microtubule defects to IQGAP3 mislocalization unresolved
    • Single cell type (cardiomyocytes)
  6. 2020 Medium

    Expanded IQGAP3 into the DNA damage response, showing it controls Rad17 and recruits the MRN complex to activate ATM/ATR signaling.

    Evidence Co-IP (IQGAP3-Rad17), knockdown, pathway activation western blots, and radioresistance assays in lung cancer

    PMID:32896617

    Open questions at the time
    • Direct vs. indirect Rad17 regulation not separated
    • Single lab without reciprocal validation
  7. 2020 High

    Defined IQGAP3 as an in vivo stem-cell regulator, marking and maintaining proliferating gastric isthmus stem cells via the Ras pathway.

    Evidence Iqgap3 reporter mouse, lineage tracing, transcriptomics, and in vivo depletion; gastric cancer Co-IP/localization for GTPase and E-cadherin/β-catenin partners

    PMID:32824461 PMID:33293280

    Open questions at the time
    • How IQGAP3 reduces cell-cell adhesion mechanistically not detailed
    • Damage-induced induction signal upstream of IQGAP3 unknown
  8. 2021 Medium

    Linked IQGAP3 to mitotic fidelity and the cell cycle through MMS19/XPD/CAK, with YAP as a transcriptional driver.

    Evidence YAP reporter assays, knockdown cell-cycle/spindle analysis, Co-IP (IQGAP3-MMS19), and XPD-knockdown epistasis rescue

    PMID:34183451

    Open questions at the time
    • Mechanism of MMS19 stabilization by IQGAP3 unresolved
    • Aneuploidy phenotype not mechanistically connected to MMS19/XPD
  9. 2022 Medium

    Identified post-transcriptional and additional transcriptional control of IQGAP3, including m6A-reader stabilization and competing PKCδ/PKCα scaffolding.

    Evidence RIP and m6A assays (IGF2BP1, SRF, FOXM1), Co-IP competitive binding (PKCδ/PKCα), hnRNPC Co-IP stabilization, and E2F1 transactivation assays

    PMID:30906629 PMID:35355828 PMID:36217548

    Open questions at the time
    • hnRNPC stabilization mechanism not biochemically defined (Low confidence)
    • Layered regulators tested largely in single cancer contexts
  10. 2022 Medium

    Positioned IQGAP3 downstream of CDC42 in a feedback loop driving Ras/ERK proliferation and survival.

    Evidence Knockdown, overexpression rescue, and Ras/ERK pathway readouts in bladder cancer

    PMID:35412170

    Open questions at the time
    • How CDC42 induces IQGAP3 expression unknown
    • Single study
  11. 2023 Medium

    Connected transcriptional induction of IQGAP3 to calcium signaling, with FOXD2 directly activating the promoter.

    Evidence ChIP, luciferase reporter, intracellular Ca2+ imaging, and knockdown in gastric adenocarcinoma

    PMID:37724892

    Open questions at the time
    • Mechanism by which IQGAP3 raises Ca2+ not defined
    • Single lab
  12. 2024 High

    Defined a PAK6-IQGAP3-RhoA contractility axis controlling actomyosin tension, invadopodia, and migration, and resolved its regulation by ubiquitination and Rac1-driven invasion.

    Evidence Co-IP (PAK6, PRKN), epistasis rescue, RhoA/Rac1 activity assays, contractility/invadopodia/migration assays, ubiquitination assays, and orthotopic HCC models

    PMID:38470497 PMID:38763182 PMID:39343867

    Open questions at the time
    • Whether PAK6 acts upstream or in complex with IQGAP3 not fully separated
    • PRKN ubiquitination sites on IQGAP3 unmapped
  13. 2025 Medium

    Revealed IQGAP3 as a node coupling Wnt/β-catenin, macrophage polarization, hearing development, and m6A regulation, with IFFO1 as a competitive inhibitor of its Cdc42 interaction.

    Evidence TurboID and Co-IP (Axin1/CK1α), IGF2BP2 sequestration with FYN/STAT1 readouts, zebrafish/KO CDC42-activity and Wnt assays, IFFO1 domain mapping and competitive binding, and WTAP/KLF2 promoter regulation with stress-fiber assays

    PMID:40239295 PMID:40634295 PMID:40830657 PMID:41317937 PMID:41467907

    Open questions at the time
    • Each mechanism rests on a single lab
    • How one scaffold coordinates these divergent pathways in vivo unresolved
  14. 2026 High

    Established mechanotransduction-driven IQGAP3 control of stemness via direct SOX2 stabilization, and a role in Marburg virus nucleocapsid transport.

    Evidence YAP1/TEAD reporters, Co-IP (IQGAP3-SOX2), SOX2 stability assays, structure-function drug screening (trimetrexate), and CRISPR IQGAP-isoform knockouts with viral transport imaging

    PMID:41661241 PMID:42251046

    Open questions at the time
    • SOX2 stabilization mechanism (degradation pathway) not fully defined
    • Viral phenotype attributed to actin modulation but not directly demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold selects among its many GTPase, signaling, and transcription-factor partners in a given cell context remains unresolved.
  • No structural model of full-length IQGAP3 or its partner-binding interfaces
  • Rules governing context-specific partner selection unknown
  • Most signaling links derive from single-lab cancer studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2 R-HSA-73894 DNA Repair 2
Partners
CDC42ERK1HRASIGF2BP2MMS19PAK6RAC1RAD17

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 IQGAP3 is a direct effector of active Rac1 and Cdc42 GTPases, associates directly with actin filaments, and accumulates asymmetrically at the distal region of axons in hippocampal neurons. Depletion of IQGAP3 impairs neurite/axon outgrowth with disorganized cytoskeleton, and IQGAP3 is indispensable for Rac1/Cdc42-promoted neurite outgrowth in PC12 cells. Protein binding assays (GTPase effector pulldown), direct actin co-sedimentation, immunofluorescence localization, siRNA knockdown with neurite outgrowth phenotypic readout Journal of cell science High 17244649
2008 IQGAP3 specifically interacts with the active GTP-bound form of Ras and regulates cell proliferation through Ras-dependent ERK activation. Knockdown inhibits proliferation and ERK activity; exogenous expression induces cell-cycle re-entry blocked by MEK inhibitor U0126, placing IQGAP3 upstream of Ras and ERK in a proliferation pathway. Co-immunoprecipitation with active Ras (GTP-bound), siRNA knockdown, MEK inhibitor epistasis (U0126), ERK activity assays, cell proliferation assays Nature cell biology High 18604197
2011 All four IQ-motifs of IQGAP3 interact with calmodulin (CaM) in the presence of calcium ions; the first IQ-motif of IQGAP3 also forms a transient interaction with myosin essential light chain (Mlc1sa) in the absence of calcium. No IQ-motifs of IQGAP3 interacted with S100B. Synthetic peptide binding assays with native gel electrophoresis, molecular modelling Bioscience reports Medium 21299499
2009 IQGAP3 is specifically expressed in proliferating hepatocytes (Ki-67+) and is highly enriched at cell-cell contacts of hepatocytes during liver regeneration and development, consistent with involvement of the IQGAP3/Ras/ERK signaling cascade in hepatocyte proliferation. Immunofluorescence, western blot, qPCR in normal, regenerating, and developing liver; comparison with IQGAP1/2 expression patterns Journal of cellular physiology Medium 19452445
2014 IQGAP3 interacts with ERK1 and enhances ERK1 phosphorylation following EGF treatment, placing IQGAP3 in the EGFR-ERK signaling axis in lung cancer cells. Co-immunoprecipitation, western blot for pERK1, EGF stimulation experiments, siRNA knockdown PloS one Medium 24849319
2015 IQGAP3 has an essential, non-redundant role in epidermal tumorigenesis; the IQGAP1 IQ-motif decoy domain inhibits oncogenic Ras-driven MAPK signaling and antagonizes tumorigenesis in vivo without disrupting normal epidermal proliferation, demonstrating IQGAP-dependent scaffolding of the Ras-MAPK pathway specifically in tumor cells. Genetically engineered human skin tissue in vivo, siRNA/shRNA knockdown, expression of dominant-negative IQGAP domain decoys, MAPK signaling assays The Journal of investigative dermatology Medium 25848980
2015 IQGAP3 loss-of-function in zebrafish impairs both cell proliferation and cell motility during embryonic development; dominant-negative FGFR1 or Ras phenotypes are rescued by co-injection of IQGAP3 mRNA, establishing IQGAP3 as a downstream regulator of the FGFR1-Ras signaling pathway. Morpholino knockdown in zebrafish, in situ hybridization, mRNA rescue experiments with dominant-negative FGFR1 and Ras constructs (genetic epistasis) Cytoskeleton (Hoboken, N.J.) High 26286209
2017 IQGAP3 promotes epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma by constitutively activating TGF-β signaling, as demonstrated by ectopic expression enhancing EMT markers and TGF-β pathway activation, and silencing reversing these effects. Ectopic overexpression, siRNA knockdown, western blot for EMT markers and TGF-β pathway components, in vitro migration/invasion assays, orthotopic xenograft mouse model Journal of translational medicine Medium 28810875
2018 During cardiomyocyte cytokinesis, IQGAP3 localizes to the cleavage furrow and stembody of the midbody. In binucleating cardiomyocytes, IQGAP3 is abnormally localized, failing to reach the midbody stembody, correlating with failed cleavage furrow ingression; this mislocalization is linked to aberrant astral microtubule distribution. Time-lapse live imaging, immunofluorescence in rat cardiomyocytes in vitro and in vivo, quantitative analysis of IQGAP3 localization at midbody vs. stembody Cardiovascular research Medium 29522098
2019 E2F1 transcriptionally activates IQGAP3 in hepatocellular carcinoma cells. IQGAP3 interacts with PKCδ and competitively inhibits the interaction between PKCδ and PKCα, resulting in PKCα phosphorylation and activation, thereby promoting cell proliferation. Co-immunoprecipitation, competitive binding assay, western blot for PKCα phosphorylation, transactivation reporter assays, HCC patient tissue correlation American journal of cancer research Medium 30906629
2020 IQGAP3 interacts with Rad17 and controls its expression to activate ATM/Chk2 and ATR/Chk1 DNA damage response signaling pathways by recruiting the MRN (Mre11-Rad50-Nbs1) complex in response to DNA damage, thereby promoting radioresistance in lung cancer. Co-immunoprecipitation (IQGAP3-Rad17 interaction), siRNA knockdown, western blot for ATM/Chk2 and ATR/Chk1 pathway activation, in vitro and in vivo radioresistance assays Cancer letters Medium 32896617
2020 IQGAP3 interacts with Rho family GTPases (including Cdc42 and Rac1), accumulates at the leading edge of migrating cells and at the cleavage furrow of dividing cells, and reduces cell-cell adhesion via interactions with E-cadherin or β-catenin proteins in gastric cancer cells. Co-immunoprecipitation, immunofluorescence localization, siRNA knockdown, overexpression morphology assays, invasion assays Biomolecules Medium 32824461
2020 IQGAP3 is a specific marker and functional regulator of proliferating isthmus stem cells in the stomach corpus. The Ras pathway is identified as a critical partner of IQGAP3 in promoting strong proliferation in these stem cells. Iqgap3 depletion impairs stem cell maintenance, and Iqgap3 expression is robustly induced following tissue damage. Iqgap3-2A-tdTomato mouse model, lineage tracing, immunofluorescence, in situ hybridization, transcriptomic analysis, Iqgap3 depletion (loss-of-function) in vivo Gut High 33293280
2021 IQGAP3 is a transcriptional target of YAP. IQGAP3 knockdown causes S-phase arrest, delayed mitotic progression, multipolar spindle formation, and aneuploidy. IQGAP3 interacts with MMS19, and IQGAP3 knockdown decreases MMS19 protein levels; XPD knockdown partially rescues reduced proliferation upon IQGAP3 knockdown, suggesting IQGAP3 modulates the cell cycle via the MMS19/XPD/CAK axis. YAP reporter assays, siRNA knockdown, flow cytometry cell-cycle analysis, immunofluorescence for spindle morphology, Co-IP (IQGAP3-MMS19 interaction), genetic epistasis (XPD knockdown rescue) Molecular cancer research : MCR Medium 34183451
2022 IGF2BP1 binds and stabilizes m6A-modified IQGAP3 transcripts, thereby upregulating IQGAP3 protein expression. Downstream IGF2BP1 targets SRF and FOXM1 also transcriptionally upregulate IQGAP3, revealing multiple layers of post-transcriptional and transcriptional IQGAP3 regulation. RNA immunoprecipitation (RIP) for IGF2BP1-IQGAP3 mRNA binding, m6A modification assays, transcription factor reporter assays, expression correlation studies iScience Medium 36217548
2022 hnRNPC directly interacts with IQGAP3 and stabilizes it to promote pancreatic cancer cell proliferation, migration, invasion, and EMT. Co-immunoprecipitation (hnRNPC-IQGAP3 direct interaction), overexpression and knockdown assays, in vivo metastasis models BioMed research international Low 35355828
2022 CDC42 promotes IQGAP3 expression, and IQGAP3 in turn activates the Ras/ERK pathway; overexpression of IQGAP3 rescues proliferation inhibition and apoptosis caused by CDC42 knockdown in bladder cancer cells, placing IQGAP3 downstream of CDC42 in this pathway. siRNA knockdown, overexpression, western blot for Ras/ERK pathway, CCK-8 proliferation, flow cytometry apoptosis, genetic epistasis (rescue experiment) Biochemical genetics Medium 35412170
2023 FOXD2 transcriptionally activates IQGAP3 by binding to its promoter region, and this FOXD2-IQGAP3 axis promotes gastric adenocarcinoma cell proliferation by inducing an increase in intracellular Ca2+ levels. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, Fluo-3 fluorescence staining for intracellular Ca2+, siRNA knockdown, western blot The Kaohsiung journal of medical sciences Medium 37724892
2024 IQGAP3 interacts with PAK6; depletion of IQGAP3 disrupts RhoA activity and actomyosin contractility, causing elongated cell morphology and inhibiting invadopodia formation and migration in triple-negative breast cancer cells. PAK6 depletion phenocopies IQGAP3 depletion, and PAK6 overexpression rescues the IQGAP3 depletion phenotype, defining a PAK6-IQGAP3-RhoA pathway driving cellular contractility. Co-immunoprecipitation (IQGAP3-PAK6 interaction), siRNA knockdown, overexpression rescue, RhoA activity assay, actomyosin contractility measurements, invadopodia assay, live-cell migration assay Cellular signalling High 38763182
2024 IQGAP3 overexpression sustains active Rac1 GTPase activity and promotes cytoskeletal remodeling in MVI+-HCC cells to enhance trans-endothelial migration. IQGAP3 also induces hepatic stellate cell (HSC) activation and disrupts HSC-endothelial interactions via upregulation of multiple cytokines, enabling an infiltrative vessel co-optive growth pattern and microvascular invasion. RNA-sequencing, proteomic analysis, co-culture modeling, Rac1 GTPase activity assays, multiplex immunofluorescence, siRNA nanoparticle delivery in orthotopic xenograft model Clinical cancer research Medium 38470497
2024 PRKN (Parkin) ubiquitinates IQGAP3 to promote its proteasomal degradation; PRKN overexpression suppresses CRC cell growth and metastasis and promotes ferroptosis, effects reversed by IQGAP3 upregulation. Co-immunoprecipitation, ubiquitination assay, western blot, siRNA/overexpression, in vivo xenograft tumor model Journal of bioenergetics and biomembranes Medium 39343867
2024 MYB transcription factor binds to the IQGAP3 promoter to transcriptionally upregulate IQGAP3 expression, and IQGAP3 mediates DNA mismatch repair/DNA damage repair pathways; silencing IQGAP3 increases 5-FU sensitivity and reversal of MYB-driven resistance requires IQGAP3. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA/overexpression, immunofluorescence for DNA damage markers, CCK-8 assay, flow cytometry Drug development research Medium 40772604
2025 IQGAP3 disrupts the Axin1-CK1α interaction (identified by TurboID proximity labeling), thereby inhibiting β-catenin phosphorylation and leading to β-catenin accumulation; IQGAP3 overexpression increases β-catenin levels and depletion reduces them. IQGAP3 is itself regulated by Wnt signaling, forming a positive feedback loop. TurboID proximity proteomics, Co-immunoprecipitation, β-catenin level assays (western blot), overexpression/knockdown, functional Wnt pathway reporter assays Oncogene Medium 40830657
2025 IQGAP3 deficiency leads to hearing loss by inhibiting CDC42 enzymatic activity and blocking the Wnt-β-catenin pathway, resulting in reduced inner ear progenitor cell proliferation (40% fewer EdU+ and 44% fewer Ki67+ cells). iqgap3 morpholino knockdown in zebrafish, IQGAP3-knockout HEK293T cells, primary mouse inner ear progenitor cell model, CDC42 activity assay, EdU/Ki67 proliferation assays, Wnt pathway assays International journal of pediatric otorhinolaryngology Medium 40239295
2025 IQGAP3 regulates macrophage polarization by binding and sequestering IGF2BP2 at the cell periphery, limiting IGF2BP2-mediated stabilization of FYN mRNA; reduced FYN expression leads to decreased STAT1 phosphorylation, driving an immunosuppressive M2-like macrophage phenotype. Co-immunoprecipitation (IQGAP3-IGF2BP2 interaction), immunofluorescence for subcellular localization, FYN mRNA stability assays, western blot for STAT1 phosphorylation, macrophage phagocytosis and T cell activation assays, xenograft model Cellular and molecular life sciences : CMLS Medium 41467907
2025 IFFO1 directly interacts with IQGAP3 through its 2A coiled-coil domain and inhibits the association of IQGAP3 with its effector Cdc42 in a dose-dependent manner, thereby suppressing IQGAP3-dependent cell migration in lung cancer cells. Co-immunoprecipitation (IFFO1-IQGAP3 interaction), domain mapping, competitive binding assay (IQGAP3-Cdc42 association dose-response to IFFO1), siRNA knockdown, migration assays Cell death & disease Medium 40634295
2025 WTAP m6A methyltransferase complex regulates IQGAP3 expression in endothelial cells via KLF2-mediated transcriptional control of the IQGAP3 promoter; IQGAP3 is identified as a key target of WTAP required for stress fiber formation in endothelial cells. RNA-seq (target identification), luciferase reporter assay (KLF2 regulation of IQGAP3 promoter/intron), siRNA knockdown of WTAP and KLF2, stress fiber quantification by VE-cadherin staining and immunofluorescence Cellular signalling Medium 41317937
2025 METTL3-catalyzed m6A modification of IQGAP3 mRNA enhances IQGAP3 stability and expression through IGF2BP2 reader protein binding to m6A-modified IQGAP3 transcripts. IQGAP3 upregulation activates TGF-β/Smad signaling and drives EMT and HCC metastasis; METTL3 or IGF2BP2 knockdown reduces m6A on IQGAP3 transcripts and decreases IQGAP3 levels and metastatic capacity. RNA immunoprecipitation (IGF2BP2-IQGAP3 mRNA binding), m6A methylation assays (METTL3 knockdown + m6A level measurement on IQGAP3 transcripts), mRNA stability assay, western blot for TGF-β/Smad pathway, in vivo lung metastasis model Pathology, research and practice Medium 40945199
2026 Matrix stiffness induces IQGAP3 expression through YAP1 and TEAD transcription factors in glioblastoma stem cells (GSCs). IQGAP3 promotes GSC self-renewal and radioresistance by binding to and stabilizing the stem cell transcription factor SOX2; IQGAP3 targeting reduces SOX2 protein levels in vitro and in vivo. Structure-function drug screening identified trimetrexate as a pharmacological disruptor of IQGAP3-SOX2 binding that sensitizes GSCs to radiotherapy. Differential gene expression (stiff vs. soft matrix), YAP1/TEAD reporter assays, Co-immunoprecipitation (IQGAP3-SOX2 binding), SOX2 protein stability assays, in vitro and in vivo GSC self-renewal/radioresistance assays, structure-function drug screening Nature communications High 42251046
2026 IQGAP3 knockout in Huh-7 cells specifically reduces Marburg virus transcription/replication efficiency, virus release, and long-distance nucleocapsid transport; IQGAP3 KO cells show reduced spatial displacement efficiency of nucleocapsids, likely through modulation of actin dynamics. CRISPR knockout cell lines (single, combined, triple IQGAP isoform KO), viral infection assays, live imaging of nucleocapsid transport, rescue by individual IQGAP re-expression Cellular and molecular life sciences : CMLS Medium 41661241

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth. Journal of cell science 143 17244649
2008 IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade. Nature cell biology 98 18604197
2014 IQGAP3 promotes EGFR-ERK signaling and the growth and metastasis of lung cancer cells. PloS one 70 24849319
2017 Role of IQGAP3 in metastasis and epithelial-mesenchymal transition in human hepatocellular carcinoma. Journal of translational medicine 55 28810875
2016 Expression and diagnostic value of CCT3 and IQGAP3 in hepatocellular carcinoma. Cancer cell international 54 27390551
2018 Cardiomyocyte binucleation is associated with aberrant mitotic microtubule distribution, mislocalization of RhoA and IQGAP3, as well as defective actomyosin ring anchorage and cleavage furrow ingression. Cardiovascular research 50 29522098
2020 Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair. Gut 48 33293280
2019 E2F1 transactivates IQGAP3 and promotes proliferation of hepatocellular carcinoma cells through IQGAP3-mediated PKC-alpha activation. American journal of cancer research 35 30906629
2016 Overexpression and biological function of IQGAP3 in human pancreatic cancer. American journal of translational research 34 28078013
2018 Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for bladder cancer. Oncotarget 33 29581849
2015 IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal Homeostasis and Tumor Progression. The Journal of investigative dermatology 29 25848980
2011 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and myosin essential light chain. Bioscience reports 28 21299499
2020 Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3. Biomolecules 27 32824461
2020 IQGAP3 interacts with Rad17 to recruit the Mre11-Rad50-Nbs1 complex and contributes to radioresistance in lung cancer. Cancer letters 26 32896617
2009 Involvement of IQGAP3, a regulator of Ras/ERK-related cascade, in hepatocyte proliferation in mouse liver regeneration and development. Journal of cellular physiology 25 19452445
2016 RNA Interference of IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Cell Proliferation and Invasion in Breast Carcinoma Cells. Oncology research 23 28281966
2021 IQGAP3, a YAP Target, Is Required for Proper Cell-Cycle Progression and Genome Stability. Molecular cancer research : MCR 21 34183451
2020 IQGAP3 promotes cancer proliferation and metastasis in high-grade serous ovarian cancer. Oncology letters 21 32724358
2018 Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria. Urologic oncology 19 30446454
2023 The Antithetic Roles of IQGAP2 and IQGAP3 in Cancers. Cancers 18 36831467
2022 CDC42 Regulates Cell Proliferation and Apoptosis in Bladder Cancer via the IQGAP3-Mediated Ras/ERK Pathway. Biochemical genetics 18 35412170
2019 IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Kaempferol-Induced Apoptosis in Breast Cancer Cells by Extracellular Signal-Regulated Kinases 1/2 (ERK1/2) Signaling Activation. Medical science monitor : international medical journal of experimental and clinical research 15 31605603
2022 hnRNPC Promotes Malignancy in Pancreatic Cancer through Stabilization of IQGAP3. BioMed research international 14 35355828
2020 Integrative Analysis of the IQ Motif-Containing GTPase-Activating Protein Family Indicates That the IQGAP3-PIK3C2B Axis Promotes Invasion in Colon Cancer. OncoTargets and therapy 14 32903879
2022 Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer. iScience 13 36217548
2015 IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development. Cytoskeleton (Hoboken, N.J.) 13 26286209
2024 Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 12 38470497
2025 IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth. Gut 11 39438124
2023 IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms. Journal of advanced research 10 36681115
2024 PAK6 acts downstream of IQGAP3 to promote contractility in triple negative breast cancer cells. Cellular signalling 8 38763182
2023 FOXD2 regulations IQGAP3 mediated Ca2+ signaling pathway to facilitate gastric adenocarcinoma cell promotion. The Kaohsiung journal of medical sciences 7 37724892
2022 lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression. BioMed research international 7 35993042
2022 IQGAP3 in clear cell renal cell carcinoma contributes to drug resistance and genome stability. PeerJ 7 36275458
2021 IQGAP3 May Serve as a Promising Biomarker in Clear Cell Renal Cell Carcinoma. International journal of general medicine 4 34285569
2024 PRKN-mediated the ubiquitination of IQGAP3 regulates cell growth, metastasis and ferroptosis in early-onset colorectal cancer. Journal of bioenergetics and biomembranes 3 39343867
2024 IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases. International journal of molecular sciences 2 38674130
2025 Intermediate filament IFFO1 negatively regulates the migration of lung cancer cells by inhibiting the IQGAP3-Cdc42 interaction. Cell death & disease 1 40634295
2025 Wnt target IQGAP3 promotes Wnt signaling via disrupting Axin1-CK1α interaction. Oncogene 1 40830657
2025 METTL3/IGF2BP2 stabilizes IQGAP3 via m6A modification to drive HCC metastasis through TGF-β/Smad signaling and EMT. Pathology, research and practice 1 40945199
2025 The lncRNA MIR4435-2HG Modulates Bladder Cancer Progression and Ferroptosis Through the IQGAP3/Ras/ERK/CREB Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41085154
2023 Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse. Methods in molecular biology (Clifton, N.J.) 1 37355533
2026 IQGAP1 and IQGAP3 are critical host factors for Marburg virus replication, nucleocapsid transport, and cell-to-cell spread. Cellular and molecular life sciences : CMLS 0 41661241
2026 IQGAP3, the overlooked oncogenic twin of IQGAP1: mapping its interactome and functional roles across cellular signaling and cancer. Cell communication and signaling : CCS 0 42063148
2026 IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2. Nature communications 0 42251046
2025 IQGAP3 deficiency leads to non-syndromic hearing loss via inhibition of CDC42 enzyme activity. International journal of pediatric otorhinolaryngology 0 40239295
2025 Transcription Factor MYB Upregulates IQGAP3 to Mediate DNA Repair and Promote 5-FU Resistance in Gastric Cancer Cells. Drug development research 0 40772604
2025 Wilms' tumor 1-associating protein regulates the stress fiber reservoirs in endothelial cells via KLF2-IQGAP3. Cellular signalling 0 41317937
2025 Targeting IQGAP3 skews macrophages polarization towards M1 phenotype and promotes antitumor immune response. Cellular and molecular life sciences : CMLS 0 41467907
2024 Retracted: lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression. BioMed research international 0 38550059
2024 IQGAP3 activates Hedgehog signaling to confer stemness and metastasis via up-regulating GLI1 in lung cancer. Scientific reports 0 39732803
2020 Intronic variant in IQGAP3 associated with hereditary neuropathy with proximal lower dominancy, urinary disturbance, and paroxysmal dry cough. Journal of human genetics 0 32341455

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