Affinage

RAB25

Ras-related protein Rab-25 · UniProt P57735

Length
213 aa
Mass
23.5 kDa
Annotated
2026-04-28
83 papers in source corpus 31 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB25 is an epithelial-enriched Rab11-family small GTPase that governs vesicular trafficking through the apical recycling endosome and late endosome/lysosome compartments, thereby controlling integrin and receptor recycling, cell polarity, cytokinetic abscission, and metabolic adaptation. RAB25 directly binds the β1 integrin cytoplasmic tail and FIP-family effectors (forming a heterotetrameric Rab25-(FIP2)₂-Rab25 complex) to route α5β1 integrin, EGFR, CaV1.2, and TGF-α to specific plasma membrane domains, with CLIC3 cooperating in retrograde transport from late endosomes (PMID:17925226, PMID:24056041, PMID:22197222, PMID:27076616, PMID:41365858). RAB25 activates AKT to promote glucose uptake, glycogen storage, and survival under nutrient stress, and its context-dependent oncogenic versus tumor-suppressive activity is determined by cell lineage, co-expressed effectors such as RCP/FIPs, and epigenetic silencing by ZEB2 acting through DNMTs and SIRT1-mediated H3K9 deacetylation (PMID:22253197, PMID:28939823, PMID:30445998, PMID:20197623). In vivo, Rab25 loss accelerates intestinal and skin tumorigenesis through dysregulated integrin trafficking, impairs cytokinetic abscission in zebrafish gastrula epithelium, disrupts epidermal barrier function by impairing keratohyalin granule maturation, and deregulates gastric pit cell fate through aberrant TGF-α secretion (PMID:20197623, PMID:31144312, PMID:33755014, PMID:36383036, PMID:41365858).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Identification of RAB25 as a novel epithelial-restricted Rab GTPase with a unique GTP-binding motif (WDTAGLE) established it as a distinct Rab11-subfamily member requiring functional characterization.

    Evidence 3'-RACE cloning, GTP-binding blot assay, and Northern blot tissue distribution from rabbit parietal cells

    PMID:8360141

    Open questions at the time
    • No effector partners identified
    • No functional assay beyond GTP binding
    • Mammalian subcellular localization not determined
  2. 1999 High

    Demonstration that Rab25 co-localizes with Rab11a at the apical recycling endosome and selectively regulates apical transcytosis and recycling (but not basolateral trafficking) in polarized epithelial cells placed it as a pathway-specific regulator of polarized membrane traffic.

    Evidence Transfection and dominant-negative expression in polarized MDCK cells with IgA transcytosis and recycling assays

    PMID:10869360 PMID:9880326

    Open questions at the time
    • Cargo identity beyond IgA not defined
    • Effector mechanism unknown
    • In vivo relevance not tested
  3. 2004 High

    The finding that RAB25 overexpression promoted cancer cell proliferation, anoikis resistance, and in vivo tumor aggressiveness via AKT activation revealed an unexpected oncogenic function for a trafficking GTPase.

    Evidence RAB25 overexpression in ovarian/breast cancer cells with proliferation, apoptosis, anoikis, and xenograft assays

    PMID:15502842

    Open questions at the time
    • Direct AKT binding not yet demonstrated
    • Mechanism connecting trafficking to AKT unclear
    • Context dependence not appreciated
  4. 2007 High

    Identification of β1 integrin as a direct cargo of Rab25 explained how vesicle trafficking controls invasive migration: Rab25 binds the β1 integrin cytoplasmic tail and delivers α5β1-containing vesicles to pseudopodial tips during 3D invasion.

    Evidence Direct pulldown with β1 integrin cytoplasmic tail, live-cell vesicle imaging, and 3D matrix invasion assays

    PMID:17925226

    Open questions at the time
    • Route through endosomal compartments not mapped
    • Role of FIP effectors in integrin delivery not tested
    • Whether other integrins are direct cargoes unknown
  5. 2010 High

    Genetic loss of Rab25 in mice accelerated intestinal tumorigenesis on ApcMin/+ background, establishing that Rab25 functions as a tumor suppressor in intestinal epithelium — the first evidence of its context-dependent dual role in cancer.

    Evidence Rab25 knockout mouse crossed to ApcMin/+ and Smad3+/- backgrounds with tumor quantification and β1 integrin localization

    PMID:20197623

    Open questions at the time
    • Molecular basis of tumor suppression vs. oncogenic activity not resolved
    • Cell-autonomous vs. non-autonomous effects not distinguished
  6. 2011 High

    The discovery that Rab25 routes active-conformation α5β1 integrin through late endosomes/lysosomes for CLIC3-dependent retrograde recycling (rather than degradation) defined a non-canonical recycling pathway that controls rear-end retraction during cell invasion.

    Evidence Photoactivation of fluorescent proteins, biochemical fractionation, CLIC3 knockdown, and 3D invasion assays

    PMID:22197222

    Open questions at the time
    • How Rab25 prevents lysosomal degradation of integrins mechanistically unclear
    • CLIC3 recruitment mechanism not defined
  7. 2012 High

    Demonstration that RAB25 directly binds and activates AKT to increase glucose uptake, ATP, and glycogen storage connected Rab25 trafficking to metabolic reprogramming and survival under nutrient stress.

    Evidence AKT binding assay, glucose uptake, ATP measurement, glycogen staining in cancer cells under nutrient deprivation

    PMID:22253197

    Open questions at the time
    • Structural basis of RAB25–AKT interaction unknown
    • Whether AKT binding requires GTP-loaded state not tested
  8. 2013 High

    The crystal structure of Rab25 in complex with FIP2 revealed a heterotetrameric architecture and subtle switch-region differences explaining the ~3-fold weaker affinity compared to Rab11a, providing the first structural basis for effector selectivity within the Rab11 subfamily.

    Evidence X-ray crystallography, isothermal titration calorimetry, and cellular co-localization of Rab25–FIP2 on endosomal membranes

    PMID:24056041

    Open questions at the time
    • Structures with other FIP family members not available
    • How differential FIP affinity translates to cargo selectivity in cells unknown
  9. 2013 High

    Multiple studies converged on Rab25's role in controlling integrin expression, tight junction composition, and F-actin organization: Rab25 knockdown decreased α5β1 integrin levels partly via ETV4-dependent transcription, while Rab25 re-expression in HNSCC blocked invasion and metastasis by reorganizing cortical F-actin.

    Evidence shRNA knockdown/rescue with Co-IP in Caco2-BBE cells; intravital imaging and 3D invasion in HNSCC mouse model

    PMID:23340300 PMID:23345591

    Open questions at the time
    • Whether ETV4 regulation is direct or indirect not fully resolved
    • Actin-regulatory mechanism downstream of Rab25 not identified
  10. 2016 High

    Rab25 was found to regulate CaV1.2 calcium channel surface expression in arterial smooth muscle by preventing lysosomal/proteasomal degradation, expanding its trafficking function beyond epithelial cells to vascular physiology.

    Evidence siRNA knockdown in cerebral artery myocytes with surface biotinylation, immunoFRET, patch-clamp electrophysiology, and myogenic tone measurement

    PMID:27076616

    Open questions at the time
    • Whether Rab25 directly binds CaV1.2 not demonstrated
    • Mechanism distinguishing lysosomal vs. proteasomal protection unclear
  11. 2017 High

    Stapled peptides disrupting the RAB25:FIP interaction validated this complex as the functional unit driving context-dependent oncogenic or tumor-suppressive outputs, providing the first pharmacological tool to dissect Rab25 effector engagement.

    Evidence Stapled peptide (RFP14) synthesis with binding assays, Co-IP disruption, and migration/proliferation assays across multiple cell contexts

    PMID:28939823

    Open questions at the time
    • In vivo pharmacokinetics not established
    • Which specific FIP family member mediates each cellular context not resolved
  12. 2018 High

    Identification of ZEB2 as a direct transcriptional repressor of RAB25 via E-box binding, DNMT-mediated promoter methylation, and SIRT1-dependent H3K9 deacetylation established the epigenetic mechanism by which EMT programs silence RAB25.

    Evidence ChIP for ZEB2 at RAB25 promoter E-boxes, bisulfite sequencing, H3K9ac ChIP, SIRT1 inhibitor treatment in conditional ZEB2 system

    PMID:30445998

    Open questions at the time
    • Whether other EMT transcription factors (Snail, Twist) similarly regulate RAB25 not tested
    • Reversibility of epigenetic silencing in tumors not explored
  13. 2019 High

    Rab25 loss in skin keratinocytes accelerated chemical carcinogenesis by dysregulating recycling of integrins β1, β4, and α6, extending the tumor-suppressor role to stratified squamous epithelium and broadening the cargo repertoire.

    Evidence Rab25 knockout mice in two-stage skin carcinogenesis model with integrin localization and recycling assays

    PMID:31144312

    Open questions at the time
    • Whether integrin α6β4 is a direct Rab25 cargo not demonstrated
    • Interaction with hemidesmosome assembly not explored
  14. 2021 High

    Zebrafish maternal-zygotic Rab25a/b mutants revealed a conserved role in cytokinetic abscission: Rab25 delivers endomembrane to midbodies, and its loss causes persistent apical bridges, altered actomyosin networks, and delayed epiboly, linking Rab25 trafficking to tissue mechanics.

    Evidence Maternal-zygotic double mutant zebrafish with live imaging of cytokinetic bridges, actomyosin quantification, and tissue mechanical measurements

    PMID:33755014

    Open questions at the time
    • Specific abscission cargo delivered by Rab25 not identified
    • Whether this role is conserved in mammalian cytokinesis unknown
  15. 2022 Medium

    RAB25 was shown to coordinate keratohyalin granule maturation and filaggrin processing in epidermis through regulation of actin dynamics, linking its trafficking function to skin barrier integrity.

    Evidence RAB25 knockout mice and siRNA in HaCaT cells with KHG immunofluorescence, actin dynamics assay, and trans-epidermal water loss measurement

    PMID:36383036

    Open questions at the time
    • Mechanism by which Rab25 regulates actin at KHGs not defined
    • Whether FIP effectors are involved in this process untested
  16. 2025 Medium

    RAB25 loss in gastric epithelium deregulates TGF-α secretory trafficking, driving EGFR-dependent foveolar hyperplasia that is rescued by TGF-α neutralization, establishing a physiological role in gastric pit cell lineage commitment.

    Evidence Rab25 KO mice, primary gastric cell culture, TGFA secretion assay, TGFA-neutralizing antibody rescue, scRNA-seq

    PMID:41365858

    Open questions at the time
    • Whether TGF-α is a direct Rab25 vesicle cargo not shown
    • Long-term cancer risk from chronic TGF-α deregulation not assessed
  17. 2025 Medium

    Discovery that RAB25 stabilizes GCN1 by inhibiting K33-ubiquitination, promoting GCN2–ATF4 ER stress signaling in alcohol-associated liver disease, revealed a non-canonical role in protein quality control beyond classical vesicle trafficking.

    Evidence Mass spectrometry, Co-IP, ubiquitination assay, GCN2/ATF4 phosphorylation analysis, in vivo ALD mouse model

    PMID:40916695

    Open questions at the time
    • Whether Rab25 GTPase activity is required for GCN1 stabilization unknown
    • Generalizability beyond ALD not tested
    • Single study without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular basis of RAB25's context-dependent switch between oncogenic and tumor-suppressive functions remains incompletely defined: it is unclear which specific FIP effector combinations, integrin cargo repertoires, and epigenetic states determine the outcome in each tissue lineage.
  • No systematic mapping of Rab25 effector complexes across tissue contexts
  • Structural basis of β1 integrin tail recognition by Rab25 unresolved
  • Role of GTP/GDP cycling kinetics in cargo selection not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0003924 GTPase activity 2
Localization
GO:0005768 endosome 3 GO:0031410 cytoplasmic vesicle 3 GO:0005886 plasma membrane 2 GO:0005764 lysosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1430728 Metabolism 2 R-HSA-1500931 Cell-Cell communication 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1 R-HSA-4839726 Chromatin organization 1
Partners
AKT1CLIC3EGFRGCN1ITGB1PKMRAB11FIP2RIN1
Complex memberships
Rab25-(FIP2)2-Rab25 heterotetramer

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 RAB25 was identified as a novel member of the Rab GTPase family with a deduced amino acid sequence showing 63% identity with Rab11, a carboxyl-terminal CCQNI motif, a novel GTP-binding site sequence (WDTAGLE), and the ability to bind GTP on blot. Its expression was restricted to epithelial tissues (gastrointestinal mucosa, lung, kidney), with enrichment in parietal cells. 3'-RACE cloning, GTP-binding blot assay, Northern blot tissue distribution The Journal of biological chemistry High 8360141
1999 Rab25 colocalizes with Rab11a in subapical vesicles of polarized MDCK epithelial cells and associates with the apical recycling endosome, which is accessible to markers internalized from both apical and basolateral membranes. Overexpression of Rab25 decreased the rate of IgA transcytosis and apical (but not basolateral) recycling, while dominant-negative Rab25T26N did not alter either process. Transfection of MDCK cells, immunofluorescence colocalization with Rab11a, dimeric IgA transcytosis assay, nocodazole treatment, dominant-negative mutant expression Molecular biology of the cell High 9880326
2000 Using inducible expression of wild-type, dominant-negative (Rab25S21N), and constitutively active (Rab25S21V) mutants in MDCK cells, Rab25 was shown to selectively regulate apical recycling and transcytosis but not basolateral transferrin recycling. Both wild-type and active Rab25 inhibited apical IgA recycling and transcytosis by >50%; GTPase-deficient Rab11aS20V inhibited transcytosis but not recycling, defining distinct functional roles. Inducible expression of GTPase mutants, IgA transcytosis assay, transferrin recycling assay in MDCK cells The Journal of biological chemistry High 10869360
2004 Forced expression of RAB25 in cancer cells markedly increased anchorage-dependent and anchorage-independent cell proliferation, prevented apoptosis and anoikis (including chemotherapy-induced), and increased in vivo tumor aggressiveness. These effects were associated with decreased expression of proapoptotic BAK and BAX and activation of the PI3K/AKT pathway. RAB25 overexpression in ovarian/breast cancer cell lines, anchorage-independent growth assay, apoptosis assay, Western blot for BAK/BAX and phospho-AKT, in vivo xenograft tumor growth Nature medicine High 15502842
2007 Rab25 directly interacts with the β1 integrin cytoplasmic tail, and this association promotes localization of integrin-recycling vesicles to pseudopodial tips and retention of a cycling pool of α5β1 at the cell front, driving invasive migration on 3D matrices. Rab25-driven tumor-cell invasion was strongly dependent on fibronectin ligation by α5β1 and the capacity of Rab25 to interact with β1 integrin. Direct interaction assay (β1 integrin cytoplasmic tail pulldown), live-cell imaging of vesicle localization, 3D matrix invasion assay, fibronectin dependence assay, interaction-deficient mutants Developmental cell High 17925226
2010 Rab25 deficiency in mice crossed onto ApcMin/+ background produced a 4-fold increase in intestinal polyps and 2-fold increase in colonic tumors, demonstrating a tumor suppressor function. Rab25-deficient mice showed decreased β1 integrin staining in lateral membranes of villus cells, indicating Rab25 regulates β1 integrin trafficking to the cell surface in intestinal epithelium. Rab25 knockout mouse model, ApcMin/+ genetic cross, Smad3+/- genetic cross, immunostaining for β1 integrin, polyp/tumor counting The Journal of clinical investigation High 20197623
2011 Rab25 directs active-conformation α5β1 integrin to late endosomes/lysosomes where, together with CLIC3, integrins are retrogradely transported and recycled to the plasma membrane at the back of invading cells rather than being degraded. CLIC3 is upregulated in Rab25-expressing cells, colocalizes with active α5β1 in late endosomes/lysosomes, and is required for release of the cell rear during migration and for maintenance of active Src signaling. Photoactivation of fluorescent proteins, biochemical fractionation, CLIC3 knockdown, 3D matrix invasion assay, active-conformation integrin antibody localization, Src signaling assay Developmental cell High 22197222
2011 Overexpression of Rab25 in non-transformed rat intestinal epithelial (RIE) cells leads to morphological transformation, anchorage-independent growth, tumor formation in nude mice, disruption of integrin-based focal adhesions, and alteration of microtubule subsets. Transformation by Rab25 (but not H-RasV12) was reversed by inhibitors of microtubule polymerization, identifying microtubule-dependent trafficking as the mechanism. Rab25 overexpression in RIE cells, soft-agar colony assay, nude mouse xenograft, focal adhesion immunostaining, microtubule inhibitor treatment, comparison with H-RasV12 transformation Cytoskeleton (Hoboken, N.J.) High 21246754
2012 RAB25 enhances survival during nutrient stress by directly binding and activating AKT, leading to increased glucose uptake, elevated cellular ATP levels, and glycogen accumulation in epithelial cancer cells—a function not previously attributed to Rab25. RAB25 overexpression/knockdown in cancer cells, AKT binding assay, glucose uptake assay, ATP measurement, glycogen staining, nutrient deprivation survival assay EMBO molecular medicine High 22253197
2012 Grhl2 transcriptionally upregulates Rab25, which in turn increases Claudin-4 protein levels and enhances its localization to tight junctions in liver progenitor epithelial cells, coordinating epithelial lumen formation in 3D culture. Grhl2 cDNA transfection, 3D cyst culture, Claudin-4 localization by immunofluorescence, Rab25 overexpression, functional tight junction assay Molecular biology of the cell Medium 22696678
2013 Crystal structure of Rab25 in complex with the C-terminal FIP2 coiled-coil domain revealed a heterotetrameric Rab25-(FIP2)2-Rab25 complex. Thermodynamic analysis showed FIP2 binds Rab25 with ~3-fold weaker affinity than Rab11a, attributable to subtle conformational differences in switch 1 and switch 2 regions. Rab25 can recruit FIP2 to endosomal membranes in cells. Crystal structure determination, isothermal titration calorimetry (ITC), cellular co-localization of Rab25 with FIP2 on endosomal membranes Biochimica et biophysica acta High 24056041
2013 Rab25 knockdown in polarized Caco2-BBE intestinal epithelial cells decreased α2-, α5-, and β1-integrin expression, with direct colocalization and co-immunoprecipitation demonstrating Rab25 directly associates with α5β1 integrins. Rab25 loss also upregulated claudin-1, increased transepithelial resistance, increased invasive behavior, and disorganized brush border microvilli. These phenotypes were rescued by reintroduction of Rab25. Rab25 regulated α5-integrin at the transcriptional level via the transcription factor ETV4. shRNA knockdown and rescue, Co-IP of Rab25 with α5β1 integrin, transepithelial resistance measurement, invasion assay, transcriptomics, ETV4 overexpression rescue Molecular biology of the cell High 23345591
2013 Rab25 regulates invasion and actin organization in head and neck squamous cell carcinoma (HNSCC): reexpression of Rab25 in a metastatic HNSCC cell line blocked invasion in 3D collagen matrix and metastasis to cervical lymph nodes in a mouse oral cancer model. Rab25 specifically affected F-actin organization at the cell surface rather than cell proliferation, apoptosis, or angiogenesis. Intravital microscopy in live animals, 3D collagen matrix invasion assay, in vivo lymph node metastasis model, F-actin staining Clinical cancer research High 23340300
2013 Rab25 regulates secretion of osteoprotegerin (OPG) at both the transcriptional and secretion level; RAB25 expression increased OPG mRNA and protein secretion from ovarian and breast cancer cells, protecting them from TRAIL-induced cell death. This effect cooperated with EGFR-mediated MAPK signaling. RAB25 overexpression/siRNA knockdown, OPG ELISA in conditioned media, TRAIL cytotoxicity assay, EGFR inhibitor combination, pharmacogenetic pathway analysis Journal of genetic syndromes & gene therapy Medium 25520884
2016 Rab25 regulates HIF-1α protein expression in an oxygen-independent manner via the ErbB2/ERK1/2 and p70S6K/mTOR pathways, requiring de novo protein synthesis rather than transcriptional upregulation. Rab25 expression induces HIF-1 transcriptional activity, increases cisplatin resistance, and confers intraperitoneal growth capacity in ovarian cancer cells. RAB25 overexpression in A2780 and SKOV3 cells, HIF-1α protein/mRNA analysis, signaling inhibitor panel (ErbB2, ERK1/2, mTOR inhibitors), HIF-1β siRNA knockdown, in vivo peritoneal carcinomatosis model Oncotarget Medium 26967059
2016 In hepatic stellate cells (HSCs), ROS-dependent Rab25 overexpression promotes the interaction of Rab25 with PI3KCIII (VPS34), directing autophagy to recognize and degrade lipid droplets during HSC activation. Rab25 siRNA blocked autophagic targeting of lipid droplets; antioxidant scavenging of ROS disrupted the Rab25-autophagy interaction. Rab25 siRNA, autophagy inhibition (Atg5 siRNA), ROS scavengers (GSH, NAC), Co-IP of Rab25 with PI3KCIII, lipid droplet staining, autophagic flux assay Redox biology Medium 28038427
2016 Rab25 expression in arterial smooth muscle cells (myocytes) promotes surface expression of CaV1.2 calcium channels by preventing their lysosomal and proteasomal degradation. Rab25 co-localizes in close spatial proximity to CaV1.2 channels (immunoFRET). Rab25 knockdown reduced CaV1.2 surface and intracellular abundance, reduced whole-cell CaV1.2 current density, and inhibited pressure- and depolarization-induced vasoconstriction in cerebral arteries. siRNA knockdown in cerebral artery myocytes, surface biotinylation assay, immunoFRET microscopy, whole-cell patch-clamp electrophysiology, myogenic tone measurement American journal of physiology. Cell physiology High 27076616
2017 Stapled peptides (RFP14) derived from the RAB-binding FIP-family inhibit RAB25:FIP complex formation, exhibit increased structural stability, binding affinity, and cell permeability. RFP14 inhibits migration and proliferation in RAB25 pro-oncogenic cell lines and augments these phenotypes in tumor-suppressive RAB25 contexts, validating the RAB25:FIP interaction as mechanistically important for context-specific oncogenic functions. All-hydrocarbon stapled peptide synthesis, binding affinity measurement, cell permeability assay, RAB25:FIP co-IP disruption assay, migration/proliferation assay in RAB25-expressing vs. RAB25-low cell lines, transcriptional profiling Nature communications High 28939823
2017 RIN1 interacts with Rab25 as a functional binding partner in renal cell carcinoma. Rab25 knockdown eliminated the augmentation of cell proliferation, migration, and invasion conferred by ectopic RIN1 expression, placing Rab25 downstream of RIN1 in activation of EGFR signaling in ccRCC. Co-IP of RIN1 with Rab25, gain/loss-of-function experiments, epistasis (Rab25 knockdown rescues RIN1 overexpression phenotype), EGFR signaling assay Cancer science Medium 28612496
2018 Rab25 increases β1 integrin levels at the plasma membrane, leading to sequential activation of EGFR and upregulation of VEGF-A expression, increased Snail and fascin expression, and epithelial-to-mesenchymal transition and cancer cell invasiveness. Snail was identified as the mediator of Rab25-induced fascin expression. Rab25 overexpression, β1 integrin surface expression assay, EGFR phosphorylation, VEGF-A ELISA, Snail/fascin Western blot, 3D invasion assay, in vivo lung metastasis model Experimental & molecular medicine Medium 29371698
2018 ZEB2 binds to E-box sequences on the RAB25 promoter and stably represses RAB25 expression through epigenetic mechanisms requiring DNA methyltransferases (DNMTs) for local DNA hypermethylation and SIRT1 for H3K9 deacetylation. SIRT1 inhibition decreased long-term repression stability but did not prevent ZEB2-mediated RAB25 downregulation directly. RAB25 partially suppresses ZEB2-mediated cell migration. Conditional ZEB2 expression system, ChIP for ZEB2 binding to RAB25 promoter E-boxes, bisulfite sequencing for DNA methylation, H3K9ac ChIP, SIRT1 inhibitor treatment, cell migration assay Epigenetics & chromatin High 30445998
2019 Rab25 interacts with β1 integrin and promotes its trafficking to the cytoplasmic membrane, leading to membrane β1 integrin-induced AKT phosphorylation and subsequent activation of the Wnt/β-catenin signaling pathway to promote cell proliferation and erlotinib resistance in NSCLC cells. Co-immunoprecipitation of Rab25 with β1 integrin, cell fractionation to assess membrane β1 integrin levels, AKT/β-catenin Western blot, lentiviral knockin/knockout, cell proliferation and drug resistance assays in vitro and in vivo Cell proliferation Medium 30848009
2019 Loss of Rab25 in skin keratinocytes causes dysregulation of integrin β1, β4, and α6 trafficking, impairs their recycling, and promotes squamous cell carcinoma development. In a two-stage mouse skin carcinogenesis model, Rab25 knockout significantly accelerated tumor generation and malignant transformation. Rab25 knockout mice, two-stage skin carcinogenesis (DMBA/TPA) model, HaCaT xenograft, integrin expression/localization immunostaining, integrin recycling assay The Journal of pathology High 31144312
2020 RAB25 interacts with EGFR and enhances EGFR recycling to the cell surface while decreasing its degradation in the cytoplasm, leading to hyperactive EGFR signaling and acquired radioresistance in lung and nasopharyngeal cancer cells. Co-IP of Rab25 with EGFR, EGFR surface expression assay, EGFR degradation kinetics, RAB25 knockdown with radiosensitivity assay in vitro and in vivo iScience Medium 32252020
2021 In zebrafish gastrula epithelium, Rab25 localizes near cytokinetic midbodies and coordinates abscission through endomembrane trafficking. Loss of maternal-zygotic Rab25a and Rab25b results in persistent apical cytokinetic bridges that fail timely abscission, causing anisotropic cell morphologies, reduced contractile actomyosin networks, slowed cell rearrangements, altered tissue viscoelastic responses, and delayed epiboly. Maternal-zygotic Rab25a/Rab25b double mutant zebrafish, live imaging of cytokinetic bridges, actomyosin network quantification, tissue mechanical measurements eLife High 33755014
2021 Rab25 co-locates on the cell membrane with PKM2 in gastric adenocarcinoma cells and can directly bind to PKM2 as shown by co-immunoprecipitation. Rab25 acts as a positive regulator of PKM2, promoting PKM2 phosphorylation (Y105) and thereby participating in the regulation of aerobic glycolysis. Co-immunoprecipitation of Rab25 with PKM2, immunofluorescence co-localization, lactate/pyruvate measurement, lentiviral overexpression/silencing Translational cancer research Medium 35116410
2022 RAB25 coordinates keratohyalin granule (KHG) maturation and filaggrin processing in epidermis by regulating actin dynamics. In HaCaT keratinocytes, RAB25 co-expresses with filaggrin-containing KHGs, and RAB25 silencing impairs KHG formation through abnormal actin dynamics. RAB25 knockout mice show disrupted stratum corneum, skin barrier dysfunction, and decreased KHG production. RAB25 knockout mice, RAB25 siRNA in HaCaT cells, KHG immunofluorescence, actin dynamics assay, trans-epidermal water loss measurement, comparison with human AD skin specimens Allergy Medium 36383036
2025 RAB25 promotes ADAMTS5 expression in ovarian cancer cells through activation of the NF-κB signaling pathway. ADAMTS5 is necessary and sufficient to stimulate ovarian cancer cell migration through fibroblast-secreted matrices, identifying it as a downstream effector of Rab25-driven invasion. RAB25 overexpression/knockdown with ADAMTS5 expression readout, NF-κB pathway inhibition, ADAMTS5 knockdown/overexpression, 3D spheroid invasion assay, selective ADAMTS5 inhibitor treatment The FEBS journal Medium 40164572
2025 RAB25 loss in gastric epithelial cells facilitates TGF-α secretion, which promotes upregulation of EGFR signaling in pit cells. In Rab25 KO mice, long-term altered TGFA secretion caused foveolar hyperplasia ameliorated by TGFA neutralization, establishing a physiological role for Rab25 in regulating gastric pit lineage commitment through control of TGFA secretory trafficking. Rab25 KO mice, mouse primary gastric cell culture, TGFA secretion assay, EGFR signaling measurement, TGFA-neutralizing antibody treatment, single-cell RNA sequencing analysis Cell death & disease Medium 41365858
2025 RAB25 interacts with GCN1, inhibits K33-ubiquitination-mediated degradation of GCN1, and thereby promotes GCN2 phosphorylation and ATF4-mediated ER stress, contributing to alcohol-associated liver disease progression. RAB25 specifically accumulated on the ER in ALD. Mass spectrometry identification of RAB25-GCN1 interaction, Co-IP assay, ubiquitination assay, GCN2/ATF4 phosphorylation Western blot, RAB25 knockdown in hepatocytes, in vivo ALD mouse model Clinical and molecular hepatology Medium 40916695
2010 The core promoter of human RAB25 contains a CRE element (-67/-58) that binds CREB, as demonstrated by EMSA and ChIP. PKA activation (forskolin) enhances chromatin accessibility at the RAB25 promoter, promotes CREB phosphorylation, recruits co-factors CBP and BRG1, and increases RAB25 expression. Deletion of the CRE abolished promoter activity. 5'-deletion luciferase reporter assay, EMSA, ChIP for CREB binding, chromatin accessibility assay (PCR-based), forskolin (PKA activator) treatment The international journal of biochemistry & cell biology Medium 21075212
2024 An APEX2 proximity labeling screen identified DENND6A as a physical interacting partner of RAB25, and this interaction affects cell migration. APEX2 proximity labeling mass spectrometry, interaction validation, cell migration assay bioRxivpreprint Low
2024 Magnetogenetic repositioning of endogenous Rab25 vesicles to the cell periphery directly drives formation of F-actin protrusions. Rab25 vesicles coordinate localization of the actin regulator FMNL1 and integrin β1 with activation of Rho GTPases at the plasma membrane to generate filopodial protrusions and promote cancer cell invasive migration in 3D matrix. Magnetogenetic manipulation of Rab25 vesicle positioning, live-cell F-actin imaging, FMNL1 and β1 integrin co-localization, Rho GTPase activation biosensor, 3D matrix invasion assay bioRxivpreprint Medium

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nature medicine 424 15502842
1999 Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Molecular biology of the cell 345 9880326
2007 Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Developmental cell 328 17925226
2011 Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Developmental cell 263 22197222
2000 Regulation of vesicle trafficking in madin-darby canine kidney cells by Rab11a and Rab25. The Journal of biological chemistry 195 10869360
1993 Identification of a small GTP-binding protein, Rab25, expressed in the gastrointestinal mucosa, kidney, and lung. The Journal of biological chemistry 130 8360141
2010 Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. The Journal of clinical investigation 121 20197623
2012 Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities in esophageal squamous cell carcinoma. Cancer research 98 22991305
2016 Autophagy regulates turnover of lipid droplets via ROS-dependent Rab25 activation in hepatic stellate cell. Redox biology 91 28038427
2012 Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25. Molecular biology of the cell 85 22696678
2010 Tumor suppressor function of Rab25 in triple-negative breast cancer. International journal of cancer 76 19795443
2010 Rab25 as a tumour suppressor in colon carcinogenesis. British journal of cancer 76 21063400
2009 The emerging role of the RAB25 small GTPase in cancer. Traffic (Copenhagen, Denmark) 69 19719478
2012 Rab25 increases cellular ATP and glycogen stores protecting cancer cells from bioenergetic stress. EMBO molecular medicine 64 22253197
2013 Rab25 regulates invasion and metastasis in head and neck cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 63 23340300
2006 Loss of RAB25 expression in breast cancer. International journal of cancer 63 16395697
2013 Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3β/Snail signaling. Carcinogenesis 58 23722651
2012 Rab25 in cancer: a brief update. Biochemical Society transactions 55 23176489
2018 Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin. Experimental & molecular medicine 50 29371698
2006 Knockdown of RAB25 expression by RNAi inhibits growth of human epithelial ovarian cancer cells in vitro and in vivo. Pathology 49 17393986
2018 MiR-577 suppresses epithelial-mesenchymal transition and metastasis of breast cancer by targeting Rab25. Thoracic cancer 42 29524309
2017 Rab25 GTPase: Functional roles in cancer. Oncotarget 40 28969096
2017 Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer. Nature communications 39 28939823
2005 Assay of Rab25 function in ovarian and breast cancers. Methods in enzymology 39 16473588
2012 Knockdown of RAB25 promotes autophagy and inhibits cell growth in ovarian cancer cells. Molecular medicine reports 36 22940905
2019 Rab25 promotes erlotinib resistance by activating the β1 integrin/AKT/β-catenin pathway in NSCLC. Cell proliferation 35 30848009
2016 Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer. Oncotarget 34 26967059
2012 The action of small GTPases Rab11 and Rab25 in vesicle trafficking during cell migration. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 34 22613965
2016 Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer. Oncotarget 33 26646320
2013 Rab25 regulates integrin expression in polarized colonic epithelial cells. Molecular biology of the cell 33 23345591
2016 Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT. Oncotarget 31 27259233
2012 Increased expression of Rab25 in breast cancer correlates with lymphatic metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 22644676
2019 Rab25 and RCP in cancer progression. Archives of pharmacal research 23 30761451
2015 Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma. Biochemical and biophysical research communications 22 25686498
2014 Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues. International journal of oncology 21 25339198
2017 RIN1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25. Cancer science 20 28612496
2013 Expression of Rab25 correlates with the invasion and metastasis of gastric cancer. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20 23592900
2020 MiR-140 inhibits classical swine fever virus replication by targeting Rab25 in swine umbilical vein endothelial cells. Virulence 19 32114898
2020 Long non-coding RNA LINC00173 serves as sponge for miR-338-3p to promote prostate cancer progression via regulating Rab25. European review for medical and pharmacological sciences 18 33015770
2014 Rab25 is responsible for phosphoinositide 3-kinase/AKT‑mediated cisplatin resistance in human epithelial ovarian cancer cells. Molecular medicine reports 18 25405658
2019 Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking. The Journal of pathology 17 31144312
2017 Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma. Scientific reports 17 29079774
2010 Is Rab25 a tumor promoter or suppressor--context dependency on RCP status? Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 20376596
2020 Rab25-Mediated EGFR Recycling Causes Tumor Acquired Radioresistance. iScience 16 32252020
2016 RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis. Epigenetics 16 27379752
2016 Rab25 influences functional Cav1.2 channel surface expression in arterial smooth muscle cells. American journal of physiology. Cell physiology 15 27076616
2015 Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 26692100
2021 The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium. eLife 14 33755014
2018 ZEB2 stably represses RAB25 expression through epigenetic regulation by SIRT1 and DNMTs during epithelial-to-mesenchymal transition. Epigenetics & chromatin 14 30445998
2010 A CRE that binds CREB and contributes to PKA-dependent regulation of the proximal promoter of human RAB25 gene. The international journal of biochemistry & cell biology 13 21075212
2017 High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy. Cancer cell international 12 28400705
2015 Cucurbit [7] uril encapsulated cisplatin overcomes resistance to cisplatin induced by Rab25 overexpression in an intraperitoneal ovarian cancer model. Journal of ovarian research 12 26384969
2013 Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase. Biochimica et biophysica acta 12 24056041
2013 High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma. Cancer medicine 12 24403269
2015 CCN3 overexpression inhibits growth of callosal projections via upregulation of RAB25. Biochemical and biophysical research communications 11 25871796
2011 Transformation of rat intestinal epithelial cells by overexpression of Rab25 is microtubule dependent. Cytoskeleton (Hoboken, N.J.) 11 21246754
2017 Knockdown of Ras-Related Protein 25 (Rab25) Inhibits the In Vitro Cytotoxicity and In Vivo Antitumor Activity of Human Glioblastoma Multiforme Cells. Oncology research 10 28281975
2012 Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma. Virchows Archiv : an international journal of pathology 10 22249560
2018 Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer. Cancer cell international 9 29515334
2015 Downregulation of Rab25 activates Akt1 in head and neck squamous cell carcinoma. Oncology letters 9 26622777
2022 RAB25 coordinates filaggrin-containing keratohyalin granule maturation and affects atopic dermatitis severity. Allergy 8 36383036
2020 RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells. Apoptosis : an international journal on programmed cell death 8 32901335
2021 Let-7d and miR-185 Impede Epithelial-Mesenchymal Transition by Downregulating Rab25 in Breast Cancer. Asian Pacific journal of cancer prevention : APJCP 6 33507713
2013 Rab25 Small GTPase Mediates Secretion of Tumor Necrosis Factor Receptor Superfamily Member 11b (osteoprotegerin) Protecting Cancer Cells from Effects of TRAIL. Journal of genetic syndromes & gene therapy 6 25520884
2025 The protease ADAMTS5 controls ovarian cancer cell invasion, downstream of Rab25. The FEBS journal 5 40164572
2023 Rab25 suppresses colon cancer cell invasion through upregulating claudin‑7 expression. Oncology reports 5 38131227
2021 Rab25 acts as an oncogene and participates in the regulation of aerobic glycolysis via PKM2 in gastric adenocarcinoma. Translational cancer research 5 35116410
2019 Rab25 Deficiency Perturbs Epidermal Differentiation and Skin Barrier Function in Mice. Biomolecules & therapeutics 5 31564077
2018 Author Correction: Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin. Experimental & molecular medicine 5 30232331
2024 Rab25 is involved in hypospadias via the β1 integrin/EGFR pathway. Experimental cell research 4 38401686
2023 Expression of Rab25 is down-regulated in the foreskin of children with hypospadias. Journal of pediatric urology 4 37246119
2021 Targeting miR-185-3p Inhibits Head and Neck Squamous Cell Carcinoma by Modulating RAB25. Frontiers in oncology 3 34868916
2016 Suppression of Tobacco Carcinogen-Induced Lung Tumorigenesis by Aerosol-Delivered Glycerol Propoxylate Triacrylate-Spermine Copolymer/Short Hairpin Rab25 RNA Complexes in Female A/J Mice. Journal of aerosol medicine and pulmonary drug delivery 3 27792477
2015 Characterization of the role Rab25 in energy metabolism and cancer using extracellular flux analysis and material balance. Methods in molecular biology (Clifton, N.J.) 3 25800844
2020 Immunohistochemical Staining for Ras-Related Protein 25 (RAB25) Associates with Luminal B Breast Cancer Subtype. The Gulf journal of oncology 2 32342915
2012 Increased Rab25 expression is not correlated with peritoneal metastasis of ovarian cancers. Cancer investigation 2 23030522
2024 Loss of RAB25 Cooperates with Oncogenes in the Transformation of Human Mammary Epithelial Cells (HMECs) to Give Rise to Claudin-Low Tumors. BioMed research international 1 38803515
2024 Deficiency in the Rab25 gene leads to a decline in male fertility and testicular injury: Impact on the regulation of germ cell proliferation and apoptosis. Experimental cell research 1 39424096
2026 RAB25 promotes hepatitis B virus-induced liver fibrosis progression through activation of the PI3K/AKT signaling pathway. Virus research 0 41651076
2026 FOXA1 and RAB25 as Biomarkers of Breast Cancer Cell Response to CYP1A1-Activated Prodrugs: Insights from CEU-938. Pharmaceuticals (Basel, Switzerland) 0 41901204
2025 RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression. Clinical and molecular hepatology 0 40916695
2025 RAB25 modulates pit cell commitment by coordinating transforming growth factor-alpha secretion from gastric epithelial cells. Cell death & disease 0 41365858
2023 A small Rho GTPase RAB25 with a potential role in chemotherapy resistance in pancreatic cancer. Cancer biomarkers : section A of Disease markers 0 36565104