Affinage

LAPTM4B

Lysosomal-associated transmembrane protein 4B · UniProt Q86VI4

Length
317 aa
Mass
35.1 kDa
Annotated
2026-06-10
90 papers in source corpus 31 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LAPTM4B is a four-transmembrane lysosomal/late-endosomal protein that governs lysosomal homeostasis, amino-acid-dependent mTORC1 signaling, and endosomal sorting to promote cell survival and tumor progression (PMID:12947545, PMID:22037872, PMID:25998567). It is required for lysosomal acidification and autophagosome maturation: its depletion raises lysosomal pH, increases membrane permeability, releases cathepsins, and triggers apoptosis, whereas its overexpression sustains autophagic flux and survival under metabolic stress (PMID:22037872). On lysosomes LAPTM4B binds the leucine transporter LAT1-4F2hc (SLC7A5-SLC3A2) and recruits it to enable luminal leucine uptake and V-ATPase-dependent mTORC1 activation (PMID:25998567); a sphingolipid-interaction motif and adjacent TM3 aspartate sense ceramide to modulate this 4F2hc engagement (PMID:29806001), and at late endosomes LAPTM4B binds ceramide to drive its export and control lysosomal membrane stability and ceramide-driven caspase-3 death signaling (PMID:26280656). On endosomes it acts as a PtdIns(4,5)P2 effector that suppresses EGFR intraluminal sorting and degradation by promoting Hrs ubiquitination—an activity opposed by PIPKIγi5/SNX5—thereby prolonging EGFR signaling (PMID:25588945), and it directly stabilizes EGFR while engaging Beclin1 to support autophagy (PMID:28479384, PMID:31410015). LAPTM4B broadly stabilizes oncogenic effectors by blocking their ubiquitin-mediated degradation: it preserves SLC7A11 against NEDD4L/ZRANB1 to suppress ferroptosis (PMID:38902268), RhoA to drive LIMK-cofilin cytoskeletal remodeling and migration (PMID:37147294), ATP1A1 against TRIM8 to confer EGFR-TKI resistance (PMID:41362742), and β-catenin via USP1/USP14 to sustain liver cancer stem-cell stemness (PMID:40171299). It also confers multidrug resistance through cytosolic doxorubicin sequestration, P-glycoprotein interaction, and PI3K/AKT activation via its N-terminal PPRP motif binding p85α (PMID:20098429, PMID:20711237, PMID:19843073). Conversely, in regulatory T cells and fibrotic tissue LAPTM4B negatively regulates TGF-β by suppressing proTGF-β1 production and by recruiting NEDD4L to degrade TGFβR2/SMAD2/3 (PMID:26126825), and its loss drives mTORC1 overactivation through a direct EC3-domain–mTOR interaction that worsens ischemia/reperfusion cardiac injury (PMID:32693673). LAPTM4B transcription is controlled by AP4, HDAC2, and an EVI1/KDM6B/H3K27me3 axis that couples it to mTOR-dependent leukemia growth (PMID:29337428, PMID:39147759, PMID:39680456).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 Medium

    Established LAPTM4B as a two-isoform, four-transmembrane intracellular-membrane protein that physically associates with integrin α6 and EGFR, providing the first link between this protein and cell-adhesion/growth-factor receptors.

    Evidence Western blot, 2D electrophoresis, immunohistochemistry, and co-IP in laminin-seeded cells

    PMID:12947545

    Open questions at the time
    • No functional consequence of the integrin/EGFR association tested
    • Interaction directness and stoichiometry not established
  2. 2003 Medium

    Showed LAPTM4B is oncogenic, answering whether its overexpression alone drives transformation by demonstrating accelerated S-phase entry and tumorigenesis in vivo.

    Evidence Overexpression in NIH3T3 with flow cytometry, growth curves, and mouse tumorigenesis assay

    PMID:12947546

    Open questions at the time
    • Molecular mechanism of Cyclin E upregulation not defined
    • Single cell-line/single-lab system
  3. 2009 Medium

    Mapped the oncogenic activity to the N-terminal PPRP motif, defining a discrete structural determinant required for proliferation, invasion, and oncoprotein induction.

    Evidence Site-directed mutagenesis with proliferation/migration/invasion assays and Western blot

    PMID:19843073

    Open questions at the time
    • Direct binding partner of PPRP not yet identified at this stage
    • Single-lab phenotypic readouts
  4. 2010 High

    Defined a multidrug-resistance mechanism, resolving how LAPTM4B confers chemoresistance via cytosolic drug sequestration, P-glycoprotein interaction, and PPRP-p85α-driven PI3K/AKT signaling.

    Evidence Reciprocal siRNA/overexpression, drug-localization imaging, co-IP, colocalization, and PI3K inhibition

    PMID:20098429 PMID:20711237

    Open questions at the time
    • Structural basis of PPRP-p85α binding not resolved
    • Relative contribution of sequestration vs. efflux vs. signaling not quantified
  5. 2011 High

    Established LAPTM4B as essential for lysosomal acidification, membrane integrity, and late-stage autophagosome maturation, explaining its pro-survival role under nutrient/hypoxic stress.

    Evidence Reciprocal knockdown/overexpression with lysosomal pH/permeability, cathepsin release, autophagy flux assays, and xenografts

    PMID:21618708 PMID:22037872

    Open questions at the time
    • Direct molecular driver of acidification not identified here
    • How autophagosome maturation is blocked mechanistically left open
  6. 2015 High

    Identified the lysosomal leucine-sensing function, answering how LAPTM4B activates mTORC1 by recruiting LAT1-4F2hc to enable luminal leucine uptake and V-ATPase-dependent signaling.

    Evidence Co-IP, colocalization, leucine uptake assay, and S6K-phosphorylation readout with knockdown/overexpression

    PMID:25998567

    Open questions at the time
    • Stoichiometry of the LAPTM4B-LAT1-4F2hc-V-ATPase assembly not defined
    • Whether leucine uptake is direct or indirect not fully resolved
  7. 2015 High

    Defined LAPTM4B as a PtdIns(4,5)P2 effector controlling EGFR fate, showing it blocks EGFR intraluminal sorting by promoting Hrs ubiquitination, counteracted by PIPKIγi5/SNX5.

    Evidence Co-IP, ubiquitination assay, EGFR degradation/signaling readouts, and binding assays

    PMID:25588945

    Open questions at the time
    • E3 ligase ubiquitinating Hrs not identified
    • Quantitative link between PIP2 levels and LAPTM4B activity not established
  8. 2015 High

    Revealed LAPTM4B as a ceramide-handling protein that exports ceramide from late endosomes, decoupling lysosomal stability from sensitivity to ceramide-driven apoptosis.

    Evidence Novel ceramide probes, reciprocal silencing/overexpression, lysosomal stability and caspase-3 assays, lipidomics

    PMID:26280656

    Open questions at the time
    • Mechanism of ceramide export (transporter vs. carrier) not defined
    • Acceptor compartment for exported ceramide unclear
  9. 2015 High

    Extended LAPTM4B to immune regulation, establishing it as a GARP-binding negative regulator of TGF-β1 production in human Tregs.

    Evidence Yeast two-hybrid, mammalian co-IP, and TGF-β1 cleavage/secretion/surface-presentation assays

    PMID:26126825

    Open questions at the time
    • Structural basis of GARP-LAPTM4B binding not resolved
    • In vivo Treg consequence not tested
  10. 2018 High

    Provided atomistic mechanism for ceramide sensing, showing a TM3 SLim motif and adjacent aspartate translate ceramide binding into altered 4F2hc engagement and mTORC signaling.

    Evidence Molecular dynamics simulation, SLim/aspartate mutagenesis, co-IP with 4F2hc, mTORC signaling assay

    PMID:29806001

    Open questions at the time
    • Simulation-predicted TM3 bending not directly observed structurally
    • In vivo relevance of ceramide-tuned mTORC not tested
  11. 2018 Medium

    Identified AP4 as a direct transcriptional activator of LAPTM4B in HCC and breast cancer, linking promoter polymorphism to LAPTM4B-driven PI3K/AKT chemoresistance and a c-Myc feedback loop.

    Evidence Luciferase reporter, EMSA, ChIP, and knockdown/overexpression phenotypes across two cancer types

    PMID:29337428 PMID:29378908

    Open questions at the time
    • Single-lab origin of both reports
    • Functional impact of the promoter polymorphism on AP4 binding not quantified
  12. 2020 High

    Defined a tumor-suppressive mTORC1-restraint function via direct EC3-domain–mTOR interaction, showing LAPTM4B loss overactivates mTORC1, represses TFEB, and worsens cardiac I/R injury.

    Evidence LAPTM4B-knockout mice, adenoviral rescue, EC3-mTOR co-IP, autophagic flux and infarct measurements, TFEB rescue

    PMID:32693673

    Open questions at the time
    • Reconciliation of mTORC1-activating (lysosomal LAT1) vs. mTORC1-suppressing (EC3-mTOR) roles not mechanistically unified
    • Direct EC3-mTOR binding interface not structurally mapped
  13. 2020 High

    Showed LAPTM4B controls the lipid composition of secreted extracellular vesicles, with SLim-dependent ILV sorting shaping sEV glycosphingolipid and ether-lipid content.

    Evidence Knockout cells, SLim-mutant expression, unbiased sEV lipidomics, ILV sorting and nanodomain stability assays

    PMID:33181324

    Open questions at the time
    • Functional consequence of altered sEV lipids on recipient cells not tested
    • Machinery sorting LAPTM4B into ILVs not identified
  14. 2022 Medium

    Connected LAPTM4B to actin-based motility, showing Cdc42-dependent filopodial localization and integrin-β1 co-trafficking that stabilizes focal adhesions and drives cancer dissemination.

    Evidence Co-IP with Cdc42 and integrin β1, confocal localization, focal-adhesion dynamics, zebrafish xenograft

    PMID:35381120

    Open questions at the time
    • Directness of Cdc42 binding vs. complex-mediated not fully resolved
    • Single-lab in vivo model
  15. 2023 Medium

    Established a recurring theme of LAPTM4B stabilizing oncogenic effectors against ubiquitination, here preserving RhoA to activate RhoA-LIMK-cofilin signaling and osteosarcoma metastasis.

    Evidence RhoA ubiquitination assay, pathway Western blots, migration and in vivo metastasis models, miR-137 regulation

    PMID:37147294

    Open questions at the time
    • E3 ligase targeting RhoA not identified
    • Mechanism by which LAPTM4B blocks RhoA ubiquitination unknown
  16. 2023 Medium

    Extended the stabilization theme to translation and stemness signaling, showing LAPTM4B stabilizes RPS9 to activate STAT3 in AML and stabilizes YAP to feed a CREB1-driven HCC stemness loop.

    Evidence Co-IP, protein-stability and ubiquitination/phosphorylation assays, fractionation, ChIP, and in vivo progression models

    PMID:36758682 PMID:37213231

    Open questions at the time
    • Mechanism of RPS9/YAP stabilization (direct vs. via deubiquitinase) not fully defined
    • Single-lab studies
  17. 2024 High

    Unified the ubiquitination-control theme across ferroptosis, drug resistance, and stemness, showing LAPTM4B protects SLC7A11 (anti-ferroptosis), ATP1A1 (EGFR-TKI resistance), and β-catenin (stemness via USP1/USP14) from degradation.

    Evidence Metabolomic/drug screens, knockout models, ubiquitination assays, co-IP of NEDD4L/TRIM8/USP partners, in vivo and patient-tissue validation

    PMID:38902268 PMID:40171299 PMID:41362742

    Open questions at the time
    • Whether a single shared biochemical activity underlies all stabilization events not determined
    • β-catenin/USP findings remain single-lab
  18. 2024 High

    Defined transcriptional and immune-microenvironment axes, showing HDAC2 and EVI1/KDM6B/H3K27me3 activate LAPTM4B transcription to drive autophagy- and mTOR-dependent malignancy, while LAPTM4B drives CXCL8-mediated MDSC recruitment.

    Evidence ChIP/ChIP-seq, H3K27me3 profiling, inhibitor and in vivo knockdown studies, CXCL8/MDSC migration assays

    PMID:38388484 PMID:39147759 PMID:39680456

    Open questions at the time
    • Direct ETV1-LAPTM4B promoter binding not confirmed
    • Interplay among the multiple transcriptional regulators not integrated
  19. 2024 Medium

    Showed LAPTM4B can suppress TGF-β signaling in fibrosis by recruiting NEDD4L to degrade TGFβR2 and active SMAD2/3, paralleling its Treg TGF-β1 role.

    Evidence Bleomycin fibrosis model with LAPTM4B deficiency/restoration, co-IP, and TGFβR2/SMAD ubiquitination assays (preprint)

    Open questions at the time
    • Preprint not yet peer reviewed
    • Reconciliation with LAPTM4B's NEDD4L-blocking role on SLC7A11 not addressed
  20. 2025 Low

    Linked CDX1-driven LAPTM4B upregulation to mTORC1 suppression and autophagy restoration, protecting against nicotine-induced cardiac remodeling.

    Evidence CDX1 and LAPTM4B perturbation with mTOR/autophagy and cardiac fibroblast/hypertrophy readouts

    PMID:40121311

    Open questions at the time
    • No direct CDX1-LAPTM4B promoter binding assay
    • Single-lab functional inference of the transcriptional axis

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LAPTM4B mechanistically reconciles opposing roles in mTORC1 signaling (lysosomal LAT1-driven activation vs. EC3-domain-mediated suppression) and in ubiquitination (protecting some substrates while recruiting NEDD4L to degrade others) remains unresolved.
  • No structural model of LAPTM4B explaining context-dependent substrate selection
  • No unifying biochemical activity proposed for its bidirectional control of degradation
  • How tissue context switches LAPTM4B between mTORC1-activating and -suppressing states is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 2
Localization
GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005886 plasma membrane 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-9612973 Autophagy 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
BECLIN1CDC42EGFRGARPMTORNEDD4LSLC3A2SLC7A5

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 LAPTM4B encodes two protein isoforms (LAPTM4B-35 at 35 kDa and LAPTM4B-24 at 24 kDa) with four putative transmembrane regions; the protein localizes predominantly to intracellular membranes; co-immunoprecipitation demonstrated that LAPTM4B forms complexes with integrin α6 and EGFR when cells are seeded on laminin substrate. Western blot, 2D electrophoresis, immunohistochemistry, co-immunoprecipitation Beijing da xue xue bao (Journal of Peking University Health Sciences) Medium 12947545
2003 LAPTM4B overexpression in NIH3T3 cells promotes cell proliferation by accelerating S-phase entry with upregulation of Cyclin E, increases attachment/spreading on fibronectin/matrigel/laminin, decreases serum dependence, and causes tumorigenesis (fibrosarcoma formation at 50% rate) in mice. Eukaryotic expression, RT-PCR, Northern/Western blot, flow cytometry, cell growth curves, scanning electron microscopy, in vivo tumorigenesis assay Beijing da xue xue bao (Journal of Peking University Health Sciences) Medium 12947546
2009 The PPRP motif in the N-terminal region of LAPTM4B-35 is critical for promoting cell proliferation, migration, and invasion, as well as upregulation of oncoproteins c-Myc, c-Jun, c-Fos, cyclin D1, and cyclin E; mutagenesis of the PPRP motif abolished these effects. Overexpression, site-directed mutagenesis, proliferation/migration/invasion assays, Western blot Cancer science Medium 19843073
2010 LAPTM4B overexpression causes sequestration of the anthracycline doxorubicin in the cytosol, delaying its appearance in the nucleus, thereby contributing to anthracycline resistance; siRNA knockdown sensitizes tumor cells to anthracyclines. siRNA knockdown, overexpression, fluorescence imaging of doxorubicin localization, cell viability assays Nature medicine High 20098429
2010 LAPTM4B-35 promotes multidrug resistance by (1) colocalizing and directly interacting with MDR1/P-glycoprotein to enhance drug efflux of doxorubicin, paclitaxel, and cisplatin, and (2) activating PI3K/AKT signaling through interaction of its N-terminal PPRP motif with the p85α regulatory subunit of PI3K. Co-IP, colocalization studies, PI3K inhibitor treatment, RNAi knockdown, drug efflux assays Oncogene High 20711237
2011 LAPTM4B is required for lysosome homeostasis and acidification; its depletion increases lysosomal membrane permeability, raises lysosomal pH, causes cathepsin release, and induces cellular apoptosis. LAPTM4B loss also blocks autophagosome maturation at late stages, rendering cells sensitive to nutrient deprivation or hypoxia. Conversely, overexpression promotes autophagic flux and cell survival during starvation and accelerates in vivo tumor growth. siRNA knockdown, overexpression, lysosomal permeability assays, pH measurement, cathepsin release assay, autophagy flux assays, in vivo xenograft Cancer research High 22037872
2011 Upregulation of LAPTM4B-35 in normal liver L02 cells activates the PI3K/AKT/Bcl-xL/Bad signaling pathway, inhibits caspase-3 activation, upregulates Bcl-2, and downregulates Bax, thereby promoting anchorage-independent proliferation, resistance to adriamycin-induced apoptosis, and 100% tumorigenesis in nude mice. Adenovirus-mediated overexpression, Western blot, apoptosis assays, in vivo xenograft Anatomical record Medium 21618708
2015 LAPTM4B is a binding partner for the leucine transporter LAT1-4F2hc (SLC7A5-SLC3A2); LAPTM4B recruits LAT1-4F2hc to lysosomes, enabling leucine uptake into lysosomes, and is required for mTORC1 activation via V-ATPase following essential amino acid or leucine stimulation. Co-IP, colocalization, leucine uptake assay, mTORC1 activation assay (S6K phosphorylation), knockdown/overexpression Nature communications High 25998567
2015 LAPTM4B is a PtdIns(4,5)P2 effector on endosomes that inhibits EGF-induced EGFR intraluminal sorting and lysosomal degradation by promoting ubiquitination of Hrs (ESCRT-0 subunit), which inhibits Hrs association with ubiquitinated EGFR, thereby enhancing and prolonging EGFR signaling. The endosomal PIP kinase PIPKIγi5 directly binds LAPTM4B and counteracts its inhibitory function by generating PtdIns(4,5)P2 and recruiting SNX5, which protects Hrs from ubiquitination. Co-IP, siRNA knockdown, ubiquitination assay, EGFR degradation assay, EGFR signaling (phospho-EGFR), binding assays The EMBO journal High 25588945
2015 LAPTM4B interacts with ceramide in late endosomes and facilitates ceramide export from late endosomal organelles, reducing late endosomal ceramide levels in parallel with and independent of acid ceramidase-dependent catabolism. LAPTM4B silencing causes late endosomal sphingolipid accumulation and lysosomal membrane destabilization but confers resistance to ceramide-driven caspase-3 activation; conversely, LAPTM4B overexpression reduces LE ceramide, stabilizes lysosomes, but sensitizes cells to drug-induced caspase-3 activation. Novel ceramide probes, LAPTM4B silencing/overexpression, lysosomal membrane stability assay, caspase-3 activation assay, lipidomics Nature chemical biology High 26280656
2015 LAPTM4B directly binds to GARP in mammalian cells (identified by yeast two-hybrid with GARP as bait in a Treg cDNA library, confirmed in mammalian co-IP); LAPTM4B decreases cleavage of proTGF-β1, reduces secretion of soluble latent TGF-β1, and reduces surface presentation of GARP·TGF-β1 complexes in regulatory T cells, but does not contribute to TGF-β1 activation. Thus LAPTM4B is a negative regulator of TGF-β1 production in human Tregs. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, TGF-β1 cleavage/secretion/surface presentation assays, siRNA knockdown The Journal of biological chemistry High 26126825
2018 Ceramide regulates LAPTM4B function through a sphingolipid interaction motif (SLim) and an adjacent aspartate residue in the third transmembrane helix (TM3): ceramide binding reduces TM3 bending via the neighboring membrane-embedded acidic residue, which facilitates LAPTM4B interaction with the amino acid transporter heavy chain 4F2hc to control mTORC signaling. Atomistic molecular dynamics simulation, mutagenesis of SLim motif and aspartate residue, co-IP of LAPTM4B with 4F2hc, mTORC signaling assay ACS central science High 29806001
2018 The transcription factor AP4 directly binds the polymorphism region of the LAPTM4B gene promoter (confirmed by luciferase reporter and EMSA), induces LAPTM4B transcription, and promotes HCC cell proliferation, metastasis, and chemotherapy resistance via LAPTM4B-mediated PI3K/AKT and caspase-dependent pathways. A positive feedback loop exists whereby LAPTM4B acting on c-Myc can in turn regulate AP4. Luciferase reporter assay, EMSA, ChIP, siRNA knockdown, overexpression, proliferation/invasion/apoptosis assays Molecular oncology Medium 29337428
2018 The transcription factor AP4 directly binds to the polymorphism region of LAPTM4B promoter and modulates its transcription (confirmed by luciferase assay and EMSA); AP4 promotes breast cancer cell proliferation, migration, invasion, and cisplatin resistance in part through upregulation of LAPTM4B. Transcription factor profiling array, luciferase reporter assay, EMSA, overexpression, siRNA knockdown, proliferation/invasion assays Molecular cancer research Medium 29378908
2020 LAPTM4B downregulation during myocardial ischemia/reperfusion causes overactivation of mTORC1 (through a direct interaction between LAPTM4B's EC3 extracellular domain and mTOR), which represses TFEB, impairing autophagic flux and worsening cardiomyocyte death; restoration of LAPTM4B or inhibition of mTORC1 by rapamycin rescues autophagic flux and reduces infarct size. LAPTM4B knockout mice, adenovirus-mediated overexpression, co-IP (LAPTM4B-mTOR interaction via EC3 domain), autophagic flux assays, lysosomal function assays, infarct size measurement, TFEB overexpression/knockdown rescue experiments Circulation research High 32693673
2020 LAPTM4B is sorted into intraluminal vesicles (ILVs) of multivesicular endosomes and released in small extracellular vesicles (sEVs); efficient ILV sorting depends on the sphingolipid interaction motif (SLim) in its third transmembrane domain. LAPTM4B controls the glycosphingolipid and ether lipid composition of sEVs: LAPTM4B knockout or SLim-deficient mutant expression causes strong enrichment of glycosphingolipids in sEVs and increased membrane nanodomain stability. LAPTM4B knockout cells, SLim mutant expression, unbiased lipidomics of sEVs, ILV sorting assays, membrane nanodomain stability assays Biochimica et biophysica acta. Molecular and cell biology of lipids High 33181324
2022 LAPTM4B-35 localizes specifically to filopodia through direct interaction with Cdc42, which promotes filopodia localization. LAPTM4B-35 stabilizes filopodia and regulates integrin β1 recycling via interaction and co-trafficking on endosomes, stimulating formation and dynamics of focal adhesions, thereby promoting cancer cell dissemination in a zebrafish xenograft model. Co-IP (LAPTM4B-35 with Cdc42 and integrin β1), confocal localization, filopodia quantification, focal adhesion dynamics assay, zebrafish xenograft model Cancer science Medium 35381120
2023 LAPTM4B promotes RhoA protein stability by suppressing ubiquitin-mediated proteasome degradation of RhoA, thereby activating the RhoA-LIMK-cofilin signaling pathway to regulate stress fiber organization and promote osteosarcoma cell migration and metastasis; miR-137 regulates LAPTM4B expression in osteosarcoma. siRNA knockdown, overexpression, RhoA ubiquitination assay, Western blot for RhoA/LIMK/cofilin pathway, migration assays, animal metastasis model, patient tissue analysis Oncogenesis Medium 37147294
2023 LAPTM4B interacts with RPS9 and positively regulates RPS9 protein stability, which in turn activates STAT3 to promote leukemia cell progression in AML. Co-IP (LAPTM4B-RPS9 interaction), protein stability assays, STAT3 activation assay, in vitro and in vivo leukemia progression assays Cellular signalling Medium 36758682
2023 LAPTM4B suppresses YAP phosphorylation and ubiquitination, preventing YAP degradation; stabilized YAP translocates to the nucleus and binds CREB1, which promotes LAPTM4B transcription, forming a positive feedback loop that maintains hepatocellular carcinoma stem cell stemness. Western blot (YAP phosphorylation/ubiquitination), nuclear/cytoplasmic fractionation, ChIP (YAP-CREB1 binding to LAPTM4B promoter), siRNA knockdown, overexpression, in vitro and in vivo stemness assays iScience Medium 37213231
2024 LAPTM4B suppresses ferroptosis in non-small cell lung cancer by inhibiting NEDD4L/ZRANB1-mediated ubiquitination and subsequent proteasomal degradation of the cystine-glutamate antiporter SLC7A11, thereby maintaining SLC7A11 protein levels and preventing ferroptotic cell death. Metabolomic screens, LAPTM4B knockout cell models, ubiquitination assays, proteasome inhibition, SLC7A11 protein stability assays, in vitro and in vivo ferroptosis assays (erastin treatment), patient tissue samples Cell death & disease High 38902268
2024 HDAC2 binds specifically to the LAPTM4B promoter at four distinct binding sites, enhancing its transcriptional activation in HCC, thereby driving autophagy-related malignant progression. ChIP-seq/ChIP (HDAC2 binding to LAPTM4B promoter), HDAC2 inhibitor treatment, overexpression/knockdown, in vitro and in vivo autophagy and proliferation assays Cell death & disease Medium 39147759
2024 ETV1 transcription factor regulates LAPTM4B expression in liver cancer stem cells; LAPTM4B promotes liver cancer stem cell self-renewal and proliferation via the Wnt1/c-Myc/β-catenin pathway, and drives CXCL8 secretion to promote myeloid-derived suppressor cell migration, affecting the tumor immune microenvironment. siRNA knockdown, overexpression, pathway inhibitors, CXCL8 secretion assays, MDSC migration assay, in vitro and in vivo tumor growth assays Cell death & disease Medium 38388484
2024 LAPTM4B promotes stemness of CD133+ liver cancer stem-like cells by activating WNT/β-catenin signaling: LAPTM4B inhibits β-catenin phosphorylation and interacts with deubiquitinating enzymes USP1 and USP14, reducing β-catenin ubiquitination and degradation, thereby enabling β-catenin nuclear translocation. Co-IP (LAPTM4B with USP1/USP14), nucleocytoplasmic separation, β-catenin ubiquitination/phosphorylation assays, Western blot, immunofluorescence, in vitro/in vivo stemness assays JHEP reports Medium 40171299
2024 In the EVI1-driven myeloid malignancy context, EVI1 directly upregulates KDM6B, which demethylates H3K27me3 to activate LAPTM4B transcription; hyperactivation of the LAPTM4B-driven mTOR pathway is crucial for the growth of EVI1-high leukemia cells, and Laptm4b knockdown partially rescues EVI1-induced abnormal hematopoiesis in vivo. Evi1-transgenic mouse model, global gene expression profiling, EVI1 binding site profiling (ChIP), H3K27me3 ChIP, KDM6B inhibition, Laptm4b knockdown in vivo, mTOR pathway assays, leukemia cell line validation The Journal of clinical investigation High 39680456
2017 Beclin1 interacts with both the N- and C-termini of LAPTM4B (independent of the Vps34 complex) and competes with EGFR for LAPTM4B binding, thereby repressing LAPTM4B-mediated EGFR activation and gastric cancer cell growth. Co-IP (Beclin1-LAPTM4B interaction), domain mapping (N- and C-termini), competition binding assay, EGFR activation assay, cell growth assay Gene Medium 28479384
2019 LAPTM4B interacts with EGFR and stabilizes it in endosomes; LAPTM4B also interacts with Beclin1, promoting autophagy initiation. LAPTM4B knockdown decreases radioresistance in nasopharyngeal cancer cells by inhibiting autophagy. Co-immunoprecipitation, confocal immunofluorescence colocalization, Western blot, flow cytometry (apoptosis), siRNA knockdown, colony formation assay OncoTargets and therapy Medium 31410015
2019 LAPTM4B activates ATG3 transcription to modulate HCC cell apoptosis and autophagy; upon starvation, LAPTM4B facilitates cell survival, inhibits apoptosis, and induces autophagic flux. LAPTM4B silencing, microarray expression profiling, real-time PCR, immunofluorescence, Western blot, in vivo xenograft Cancer management and research Low 31118766
2024 LAPTM4B confers resistance to EGFR-TKIs in NSCLC by interacting with ATP1A1 and facilitating its endocytosis while preventing its proteasomal degradation by suppressing TRIM8-mediated K63-linked ubiquitination of ATP1A1, thereby stabilizing ATP1A1 and enhancing lysosomal acidification and EGFR phosphorylation/downstream signaling. EGFR-TKIs impair WWP2-mediated proteasomal degradation of LAPTM4B, increasing LAPTM4B levels. Co-IP (LAPTM4B-ATP1A1 interaction), K63-ubiquitination assay, endocytosis assay, lysosomal acidification measurement, EGFR phosphorylation assay, in vitro and in vivo drug resistance assays, high-content drug screen, patient tissue analysis International journal of biological sciences High 41362742
2024 LAPTM4B recruits the E3 ubiquitin ligase NEDD4L to endosomes, leading to increased ubiquitin-mediated proteasomal degradation of TGFβR2 and active SMAD2/3, thereby blocking the TGF-β/SMAD signaling pathway and alleviating pulmonary fibrosis. In vivo bleomycin-induced fibrosis model (LAPTM4B deficiency and restoration), co-IP (LAPTM4B-NEDD4L), ubiquitination/degradation assays for TGFβR2 and SMAD2/3, TGF-β signaling readouts bioRxivpreprint Medium
2015 LAPTM4B protein is ubiquitinated in bovine granulosa cells: affinity-purified His-tagged LAPTM4B overexpressed in HEK cells showed that the 31.5 kDa isoform represents the ubiquitinated form of the 26.3 kDa native protein, and the ubiquitinated form is differentially expressed during follicular development. Immunoblotting with anti-LAPTM4B antibody, His-tag affinity purification, identification of ubiquitinated vs. non-ubiquitinated isoforms Journal of ovarian research Low 25881887
2025 CDX1 transcription factor promotes LAPTM4B transcription, and CDX1-mediated LAPTM4B upregulation inhibits mTORC1 pathway activation, thereby alleviating autophagic flux impairment and protecting against nicotine-induced cardiac fibroblast activation and cardiomyocyte hypertrophy. CDX1 overexpression/knockdown, LAPTM4B knockdown, mTOR pathway assays, autophagic flux assays, cardiac fibroblast activation and hypertrophy readouts Scientific reports Low 40121311

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nature medicine 291 20098429
2015 LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation. Nature communications 170 25998567
2003 Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene 148 12902989
2020 Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury. Circulation research 113 32693673
2010 LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene 104 20711237
2004 The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression. Cancer letters 88 15911104
2015 miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression. Oncotarget 86 25714029
2015 LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation. The EMBO journal 80 25588945
2011 Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer research 76 22037872
2017 Long Noncoding RNA HCAL Facilitates the Growth and Metastasis of Hepatocellular Carcinoma by Acting as a ceRNA of LAPTM4B. Molecular therapy. Nucleic acids 74 29246322
2010 Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer letters 70 20202745
2018 Simultaneous Amelioratation of Colitis and Liver Injury in Mice by Bifidobacterium longum LC67 and Lactobacillus plantarum LC27. Scientific reports 67 29760423
2018 Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 mitigate alcoholic steatosis in mice by inhibiting LPS-mediated NF-κB activation through restoration of the disturbed gut microbiota. Food & function 65 30010169
2016 LAPTM4B: an oncogene in various solid tumors and its functions. Oncogene 65 27212036
2019 Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 simultaneously alleviate high-fat diet-induced colitis, endotoxemia, liver steatosis, and obesity in mice. Nutrition research (New York, N.Y.) 57 30982555
2009 LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells. Cancer science 54 19843073
2007 Overexpression of LAPTM4B-35 closely correlated with clinicopathological features and post-resectional survival of gallbladder carcinoma. European journal of cancer (Oxford, England : 1990) 54 17276673
2015 LAPTM4B facilitates late endosomal ceramide export to control cell death pathways. Nature chemical biology 52 26280656
2012 SERPINA6, BEX1, AGTR1, SLC26A3, and LAPTM4B are markers of resistance to neoadjuvant chemotherapy in HER2-negative breast cancer. Breast cancer research and treatment 52 23203637
2006 Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer. Annals of oncology : official journal of the European Society for Medical Oncology 44 17074969
2010 LAPTM4B overexpression is a novel predictor of epithelial ovarian carcinoma metastasis. International journal of cancer 38 20857494
2003 [Identification and characterization of LAPTM4B encoded by a human hepatocellular carcinoma-associated novel gene]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 37 12947545
2018 A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction. ACS central science 34 29806001
2011 Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells. Surgery 34 21429547
2007 Relationship between LAPTM4B gene polymorphism and susceptibility of colorectal and esophageal cancers. Annals of oncology : official journal of the European Society for Medical Oncology 34 17965115
2011 Correlation of LAPTM4B polymorphisms with cervical carcinoma. Cancer 33 21656743
2009 Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro. American journal of surgery 32 19954766
2012 The amplified cancer gene LAPTM4B promotes tumor growth and tolerance to stress through the induction of autophagy. Autophagy 27 22301992
2011 Relationship between LAPTM4B gene polymorphism and susceptibility of primary liver cancer. Annals of oncology : official journal of the European Society for Medical Oncology 27 22156622
2024 LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer. Cell death & disease 26 38902268
2012 Association of LAPTM4B gene polymorphism with breast cancer susceptibility. Cancer epidemiology 26 22270081
2003 [Effects of the novel gene, LAPTM4B, highly expression in hepatocellular carcinoma on cell proliferation and tumorigenesis of NIH3T3 cells]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 26 12947546
2015 LAPTM4B down regulation inhibits the proliferation, invasion and angiogenesis of HeLa cells in vitro. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 25 26383850
2010 Overexpression of LAPTM4B-35 in cervical carcinoma: a clinicopathologic study. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 25 20881850
2024 HDAC2 promotes autophagy-associated HCC malignant progression by transcriptionally activating LAPTM4B. Cell death & disease 24 39147759
2018 AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity. Molecular oncology 24 29337428
2019 LAPTM4B facilitates tumor growth and induces autophagy in hepatocellular carcinoma. Cancer management and research 23 31118766
2015 Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells. The Journal of biological chemistry 23 26126825
2025 LAPTM4B as a key regulator in the copper-induced endoplasmic reticulum-lysosome interplay disorder in duck liver and the protective role of baicalin. Journal of animal science and biotechnology 21 40887645
2017 LAPTM4B Predicts Axillary Lymph Node Metastasis in Breast Cancer and Promotes Breast Cancer Cell Aggressiveness in Vitro. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 28245476
2011 Upregulation of LAPTM4B-35 promotes malignant transformation and tumorigenesis in L02 human liver cell line. Anatomical record (Hoboken, N.J. : 2007) 21 21618708
2012 Correlation of LAPTM4B polymorphisms with gallbladder carcinoma susceptibility in Chinese patients. Medical oncology (Northwood, London, England) 19 22302286
2020 LAPTM4B controls the sphingolipid and ether lipid signature of small extracellular vesicles. Biochimica et biophysica acta. Molecular and cell biology of lipids 18 33181324
2019 LAPTM4B knockdown increases the radiosensitivity of EGFR-overexpressing radioresistant nasopharyngeal cancer cells by inhibiting autophagy. OncoTargets and therapy 18 31410015
2014 LAPTM4B-35 protein as a potential therapeutic target in gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 25416438
2011 Correlation of LAPTM4B polymorphisms with hepatocellular carcinoma in Chinese patients. Medical oncology (Northwood, London, England) 18 22207410
2024 LAPTM4B-mediated hepatocellular carcinoma stem cell proliferation and MDSC migration: implications for HCC progression and sensitivity to PD-L1 monoclonal antibody therapy. Cell death & disease 17 38388484
2022 LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics. Cancer science 17 35381120
2018 The Transcription Factor AP4 Promotes Oncogenic Phenotypes and Cisplatin Resistance by Regulating LAPTM4B Expression. Molecular cancer research : MCR 17 29378908
2005 [Relationship between LAPTM4B gene polymorphism and susceptibility of lung cancer]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 17 15968325
2017 Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells. Gene 16 28479384
2018 Detection of urinary survivin using a magnetic particles-based chemiluminescence immunoassay for the preliminary diagnosis of bladder cancer and renal cell carcinoma combined with LAPTM4B. Oncology letters 15 29725479
2023 miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma. Oncogenesis 14 37147294
2013 Association of LAPTM4B gene polymorphism with nasopharyngeal carcinoma susceptibility in a Chinese population. Medical oncology (Northwood, London, England) 14 23345117
2023 Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity. Frontiers in pharmacology 12 36937841
2019 Co-expression of HIF-1α, MDR1 and LAPTM4B in peripheral blood of solid tumors. PeerJ 11 30746305
2012 Expression of genes FOLR1, BAG1 and LAPTM4B in functioning and non-functioning pituitary adenomas. Folia neuropathologica 11 23023342
2010 Expression of LAPTM4B in gallbladder carcinoma cells: the role in invasive potential. Hepato-gastroenterology 11 20583413
2022 Role and mechanism of action of LAPTM4B in EGFR-mediated autophagy. Oncology letters 10 35242237
2015 Predictive significance of combined LAPTM4B and VEGF expression in patients with cervical cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 26526574
2014 Relationship Between LAPTM4B Gene Polymorphism and Susceptibility of Malignant Melanoma in Chinese Patients. Translational oncology 10 25389459
2015 Differential expression of lysosome-associated protein transmembrane-4 beta (LAPTM4B) in granulosa cells of ovarian follicles and in other bovine tissues. Journal of ovarian research 9 25881887
2015 The relationship between LAPTM4B polymorphisms and cancer risk in Chinese Han population: a meta-analysis. SpringerPlus 9 25932367
2006 [Relationship between LAPTM4B gene polymorphism and susceptibility of lung cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 9 21144292
2023 LAPTM4B promotes AML progression through regulating RPS9/STAT3 axis. Cellular signalling 8 36758682
2023 LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma. iScience 8 37213231
2020 Long Non-Coding RNA TP73-AS1 Promotes the Development of Lung Cancer by Targeting the miR-27b-3p/LAPTM4B Axis. OncoTargets and therapy 8 32764992
2019 Helicobacter pylori infection promotes epithelial-to-mesenchymal transition of gastric cells by upregulating LAPTM4B. Biochemical and biophysical research communications 8 31084933
2016 Targeting a novel cancer-driving protein (LAPTM4B-35) by a small molecule (ETS) to inhibit cancer growth and metastasis. Oncotarget 7 27542271
2015 Lentivirus-mediated RNA Interference Targeting LAPTM4B Inhibits Human Ovarian Cancer Cell Invasion In Vitro. Chemical biology & drug design 7 26247403
2014 Association between LAPTM4B gene polymorphism and breast cancer susceptibility in an Iranian population. Medical oncology (Northwood, London, England) 7 25001088
2024 LAPTM4B enhances the stemness of CD133+ liver cancer stem-like cells via WNT/β-catenin signaling. JHEP reports : innovation in hepatology 5 40171299
2016 Association between LAPTM4B gene polymorphism and prostate cancer susceptibility in an Iranian population. Molecular & cellular oncology 5 28090574
2024 Evi1 governs Kdm6b-mediated histone demethylation to regulate the Laptm4b-driven mTOR pathway in hematopoietic progenitor cells. The Journal of clinical investigation 4 39680456
2021 LAPTM4B promotes the progression of nasopharyngeal cancer. Bosnian journal of basic medical sciences 4 32651973
2021 [Serum LAPTM4B-35 protein as a novel diagnostic marker for hepatocellular carcinoma]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 4 34393233
2021 LAPTM4B promotes the progression of bladder cancer by stimulating cell proliferation and invasion. Oncology letters 4 34589144
2019 Clinical impact of circulating LAPTM4B-35 in pancreatic ductal adenocarcinoma. Journal of cancer research and clinical oncology 4 30778748
2014 LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese populations: a meta-analysis. BMC genetics 4 24746178
2021 Noninvasively visualize the expression of LAPTM4B protein using a novel 18F-labeled peptide PET probe in hepatocellular carcinoma. Nuclear medicine and biology 3 34214768
2013 LAPTM4B-35 protein is a weak tumor-associated antigen candidate. Experimental and therapeutic medicine 3 24396432
2019 LAPTM4B-35 expression is associated with pathological grades and clinical stages in salivary adenoid cystic carcinoma. Oncology letters 2 31897144
2018 LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas. Cancer chemotherapy and pharmacology 2 29770955
2017 LAPTM4B*2 allele is associated with the development of papillary thyroid carcinoma in Chinese women. Oncology letters 2 28927096
2025 CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B. Scientific reports 1 40121311
2022 Screening of four key genes in esophageal carcinoma based on TCGA and GEO data and verification of anti-proliferative effect of LAPTM4B knockdown in esophageal carcinoma cells invitro. Archives of biochemistry and biophysics 1 35863479
2026 LAPTM4B Confers Resistance to EGFR-TKIs by Suppressing the Proteasomal Degradation of ATP1A1 in Non-small Cell Lung Cancer. International journal of biological sciences 0 41362742
2026 Huoxue Jiedu formula attenuates myocardial ischemia-reperfusion injury by modulating LAPTM4B/mTORC1/TFEB pathway-mediated autophagic flux. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 42184497
2026 miR-489 induces immunogenic cell death in breast cancer by targeting LAPTM4B. Frontiers in oncology 0 42245684
2021 [Effect of Laptm4b Deletion on Hematopoietic Stem and Progenitor Cells Homeostasis in Mice]. Zhongguo shi yan xue ye xue za zhi 0 34627451

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