Affinage

RAB25

Ras-related protein Rab-25 · UniProt P57735

Length
213 aa
Mass
23.5 kDa
Annotated
2026-06-10
83 papers in source corpus 34 papers cited in narrative 35 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

RAB25 is an epithelial-enriched Rab11-subfamily small GTP-binding protein that governs selective apical membrane recycling and the trafficking of cargo to and from the cell surface (PMID:8360141, PMID:9880326). It localizes to subapical recycling endosomes where it colocalizes with Rab11a and, in a GTP-state-dependent manner, restrains apical IgA recycling and basolateral-to-apical transcytosis without affecting basolateral recycling (PMID:9880326, PMID:10869360). Mechanistically, RAB25 binds the FIP2 effector—captured in a heterotetrameric Rab25-(FIP2)2-Rab25 crystal structure—and recruits it to endosomal membranes (PMID:24056041), and it directly engages the β1 integrin cytoplasmic tail to position α5β1-integrin-bearing recycling vesicles at invasive cell protrusions, driving fibronectin-dependent 3D invasion (PMID:17925226). RAB25 coordinates actin-rich protrusion formation by directing FMNL1 and β1 integrin to the periphery alongside Rho GTPase activation, and routes active integrin through CLIC3-dependent late-endosomal recycling for cell-rear release during migration (PMID:22197222). Beyond trafficking, RAB25 binds and activates AKT to enhance glucose uptake and glycogen storage during nutrient stress (PMID:22253197) and suppresses mitochondrial apoptosis by lowering proapoptotic BAX/BAK priming (PMID:15502842, PMID:32901335). It controls surface abundance of receptors and channels including EGFR (PMID:32252020) and CaV1.2 in smooth muscle (PMID:27076616), and coordinates cytokinetic abscission via endomembrane trafficking during epithelial morphogenesis (PMID:33755014). RAB25's role in cancer is sharply context-dependent: it acts as an oncogene promoting integrin- and EGFR-driven invasion and metastasis in some tissues (PMID:17925226, PMID:29371698), yet behaves as a tumor suppressor in intestinal, esophageal, and skin epithelia, where its loss accelerates tumorigenesis and impairs integrin trafficking (PMID:20197623, PMID:22991305, PMID:31144312). Its expression is set by transcriptional inputs including CREB (PMID:21075212), Grhl2 (PMID:22696678), and ZEB2-mediated epigenetic repression (PMID:30445998).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 Medium

    Established RAB25 as a bona fide GTP-binding protein and defined its restricted epithelial expression, framing it as a tissue-specific Rab GTPase rather than a ubiquitous trafficking factor.

    Evidence 3'-RACE cloning, GTP-binding blot assay, and Northern blot across tissues

    PMID:8360141

    Open questions at the time
    • No effector or subcellular compartment identified
    • GTP hydrolysis/cycling kinetics not measured
  2. 2000 High

    Localized RAB25 to apical recycling endosomes and showed it selectively regulates apical recycling and transcytosis but not basolateral recycling, establishing it as a polarity-specific trafficking regulator with GTP-state-dependent activity.

    Evidence Wild-type, dominant-negative, and constitutively active mutant expression in polarized MDCK cells with quantitative IgA transcytosis and transferrin recycling assays

    PMID:10869360 PMID:9880326

    Open questions at the time
    • Effectors mediating apical selectivity not yet identified
    • Cargo beyond IgA not surveyed
  3. 2004 High

    Connected RAB25 to cancer phenotypes by showing forced expression drives proliferation, resists anoikis, and activates PI3K/AKT while lowering BAK/BAX, recasting a trafficking GTPase as an oncogenic survival factor.

    Evidence Forced expression, soft agar and in vivo tumor assays, BAK/BAX Western blots, PI3K/AKT pathway analysis in ovarian and breast models

    PMID:15502842

    Open questions at the time
    • Direct molecular link between RAB25 trafficking and AKT activation not resolved here
    • Mechanism of BAK/BAX downregulation unclear
  4. 2007 High

    Defined the molecular basis of RAB25-driven invasion by showing it directly binds the β1 integrin tail and positions α5β1-recycling vesicles at pseudopodial tips, linking trafficking to fibronectin-dependent migration.

    Evidence Co-IP, live-cell vesicle imaging, 3D fibronectin invasion assays, and interaction mutants

    PMID:17925226

    Open questions at the time
    • Whether binding is direct GTP-dependent contact not fully dissected
    • Other integrin cargo not addressed
  5. 2010 High

    Revealed the context-dependence of RAB25 by establishing it as a tumor suppressor in intestinal neoplasia, showing its loss increases polyp/tumor burden and reduces β1 integrin at lateral membranes—opposite to its oncogenic role elsewhere.

    Evidence Rab25 knockout mice on ApcMin/+ and Smad3+/- backgrounds, tumor counting, β1 integrin IHC; separately, CRE/CREB promoter mapping by EMSA/ChIP

    PMID:20197623 PMID:21075212

    Open questions at the time
    • Molecular determinant of tissue-specific oncogenic vs suppressive switch unknown
    • Link between integrin mislocalization and tumor suppression mechanistic detail incomplete
  6. 2011 High

    Extended the integrin-trafficking model by showing RAB25 sorts active α5β1 to late endosomes for CLIC3-dependent retrograde recycling at the cell rear, and demonstrated transformation requires microtubule-dependent trafficking.

    Evidence Photoactivation microscopy, biochemical fractionation, CLIC3 knockdown/rescue, 3D/organotypic invasion; RIE-cell transformation with microtubule inhibitors

    PMID:21246754 PMID:22197222

    Open questions at the time
    • How RAB25 diverts integrin from degradation to recycling not fully resolved
    • CLIC3 regulation by RAB25 only correlative on expression
  7. 2012 Medium

    Broadened RAB25 function to metabolism, junction biology, and additional cancer contexts—it binds/activates AKT to boost glycolysis and glycogen, is a Grhl2 target promoting claudin-4 junctions, and suppresses ESCC invasion via FAK-ERK signaling.

    Evidence AKT binding and metabolic flux assays; Grhl2 transfection and 3D cyst cultures; lentiviral gain/loss with FAK-Raf-MEK-ERK readouts and promoter methylation analysis

    PMID:22253197 PMID:22696678 PMID:22991305

    Open questions at the time
    • Whether AKT binding is direct or trafficking-mediated unresolved
    • Mechanism connecting RAB25 to claudin levels unclear
  8. 2013 High

    Provided structural and mechanistic depth: solved the RAB25-FIP2 complex, mapped RAB25 control of integrin expression via ETV4, and added OPG secretion and F-actin/metastasis roles, consolidating the effector and cargo network.

    Evidence Crystal structure plus ITC; shRNA knockdown/rescue with ETV4 epistasis in Caco2-BBE; OPG ELISA with EGFR/MAPK inhibition; HNSCC re-expression with intravital imaging and metastasis scoring

    PMID:23340300 PMID:23345591 PMID:24056041 PMID:25520884

    Open questions at the time
    • How FIP2 binding translates to specific cargo routing not directly tested
    • ETV4 regulation by RAB25 mechanism unclear
  9. 2016 Medium

    Showed RAB25 controls surface levels of signaling receptors and channels and engages stress pathways—stabilizing HIF-1α via ErbB2/mTOR, controlling CaV1.2 in arterial myocytes, and driving autophagic lipid-droplet turnover with PI3KCIII.

    Evidence HIF-1α protein/pathway inhibitor analysis with in vivo cisplatin models; immunoFRET, biotinylation, patch-clamp and myography for CaV1.2; Co-IP and ROS/autophagy assays in hepatic stellate cells

    PMID:26967059 PMID:27076616 PMID:28038427

    Open questions at the time
    • Whether RAB25 directly traffics CaV1.2 or acts indirectly not fully distinguished
    • RAB25-PI3KCIII binding only by Co-IP
  10. 2017 High

    Validated the RAB25:FIP interface as a druggable, phenotype-determining interaction by showing stapled peptides disrupt the complex and produce context-specific outcomes consistent with RAB25's dual oncogenic/suppressive behavior.

    Evidence All-hydrocarbon stapled peptide (RFP14) with binding, complex-inhibition, permeability, and migration/proliferation assays plus transcriptional profiling

    PMID:28939823

    Open questions at the time
    • In vivo efficacy not established
    • Full downstream consequences of FIP displacement not mapped
  11. 2018 Medium

    Resolved transcriptional and downstream signaling control: ZEB2 epigenetically represses RAB25, while RAB25 elevates β1 integrin/EGFR/VEGF-A to drive Snail-fascin-dependent EMT and metastasis.

    Evidence ChIP, bisulfite sequencing, H3K9Ac ChIP and SIRT1/DNMT inhibition for ZEB2 repression; pathway Westerns, Snail knockdown epistasis, and in vivo lung metastasis for the EMT axis

    PMID:29371698 PMID:30445998

    Open questions at the time
    • Reconciliation of EMT-promoting vs claudin-stabilizing roles unresolved
    • Direct vs indirect VEGF-A induction unclear
  12. 2019 Medium

    Reinforced both oncogenic signaling and tumor-suppressive integrin trafficking arms—RAB25-β1 integrin-AKT-Wnt drives NSCLC proliferation and erlotinib resistance, while RAB25 loss dysregulates integrin recycling to promote skin SCC.

    Evidence Co-IP, fractionation, lentiviral gain/loss and xenografts in NSCLC; Rab25 KO two-stage skin carcinogenesis with integrin trafficking readouts

    PMID:30848009 PMID:31144312

    Open questions at the time
    • Tissue determinant of opposite integrin outcomes not identified
    • β1-integrin-to-Wnt mechanistic link incomplete
  13. 2020 Medium

    Connected RAB25 receptor recycling to therapy resistance and confirmed an apoptosis-suppressing role upstream of mitochondrial permeabilization, identifying actionable vulnerabilities.

    Evidence Co-IP and EGFR recycling/degradation with radiosensitivity assays; BH3 profiling, BCL-2 family Westerns, and RNAi/RFP14 chemosensitization in ovarian cancer

    PMID:32252020 PMID:32901335

    Open questions at the time
    • Direct biochemical target among BCL-2 proteins not pinpointed
    • EGFR recycling step regulated by RAB25 not structurally defined
  14. 2021 High

    Demonstrated a developmental morphogenetic role—RAB25 coordinates cytokinetic abscission and actomyosin-dependent cell rearrangement during epithelial epiboly—and added a PKM2-glycolysis arm in gastric cancer.

    Evidence Maternal-zygotic rab25a/b mutant zebrafish with live imaging and tissue mechanics; Co-IP/colocalization and PKM2-Y105 phosphorylation in gastric adenocarcinoma

    PMID:33755014 PMID:35116410

    Open questions at the time
    • Effectors linking RAB25 to midbody abscission unidentified
    • How RAB25 promotes PKM2 phosphorylation mechanistically unclear
  15. 2023 Medium

    Refined the tumor-suppressive mechanism in colon cancer, showing RAB25 stabilizes claudin-7 to inactivate EGFR and reduce Snail, integrating junction control with receptor signaling.

    Evidence RAB25 overexpression, claudin-7 knockdown epistasis, 3D invasion assays, and claudin-7 protein-stability assays

    PMID:38131227

    Open questions at the time
    • Mechanism of claudin-7 stabilization not defined
    • Relation to EMT-promoting role in other tissues unresolved
  16. 2025 Medium

    Expanded RAB25 mechanisms into ER-localized stress signaling, secreted protease induction, and lineage control—stabilizing GCN1 to drive ATF4 ER stress in liver, inducing ADAMTS5 via NF-κB to promote ovarian invasion, and restraining TGF-α/EGFR-driven gastric pit lineage commitment.

    Evidence MS/Co-IP and K33-ubiquitination/GCN2-ATF4 assays in ALD; NF-κB reporter and ADAMTS5 rescue in ovarian 3D invasion; Rab25 KO mice with single-cell RNA-seq and TGF-α neutralization

    PMID:40164572 PMID:40916695 PMID:41365858

    Open questions at the time
    • ER-localized vs endosomal RAB25 pool regulation unclear
    • How RAB25 shields GCN1 from ubiquitination mechanistically undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • What single molecular determinant switches RAB25 between oncogenic and tumor-suppressive behavior across epithelia, and how its GTP-cycling state selects among the many cargoes (integrins, EGFR, CaV1.2, claudins) and effectors (FIP2, CLIC3, AKT, GCN1) it engages, remains unresolved.
  • No unifying model for context-dependent oncogenic/suppressive duality
  • GEF/GAP regulators of RAB25 not identified in the corpus
  • Cargo-selection rules among competing effectors undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 3 GO:0031410 cytoplasmic vesicle 3 GO:0005764 lysosome 2 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
AKT1CLIC3EGFRGCN1ITGB1PIK3C3PKM2RAB11FIP2
Complex memberships
Rab25-(FIP2)2-Rab25 heterotetramer

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 RAB25 was identified as a novel small GTP-binding protein with a unique carboxyl-terminal CCQNI motif and a novel GTP-binding site sequence (WDTAGLE); recombinant Rab25 was able to bind GTP on blot. Its expression was restricted to gastrointestinal mucosa, lung, and kidney, with enrichment in parietal cells. 3'-RACE cloning, GTP-binding blot assay, Northern blot The Journal of biological chemistry Medium 8360141
1999 Rab25 localizes to subapical vesicles and colocalizes with Rab11a in the apical recycling endosome of polarized MDCK cells. Overexpression of Rab25 decreased the rate of IgA transcytosis and of apical (but not basolateral) recycling. The dominant-negative Rab25T26N did not alter apical recycling or transcytosis. Transfection in MDCK cells, immunofluorescence colocalization, quantitative transcytosis/recycling assays, dominant-negative and wild-type constructs Molecular biology of the cell High 9880326
2000 Using inducible expression of wild-type, dominant-negative, and constitutively active mutants, both Rab25 wild-type (S21V) and the constitutively active mutant inhibited apical IgA recycling and transcytosis by >50% but had no effect on basolateral transferrin recycling. The GTPase-deficient Rab11aS20V inhibited basolateral-to-apical transcytosis but not recycling, establishing distinct roles for GTP-binding state in apical trafficking. Inducible expression of wild-type, dominant-negative (Rab25S21V), and constitutively active mutants in MDCK cells; quantitative IgA transcytosis and transferrin recycling assays 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, and increased tumor aggressiveness in vivo. The inhibition of apoptosis was associated with decreased expression of proapoptotic BAK and BAX, and activation of the PI3K/AKT pathway. Transfection/forced expression, soft agar assays, in vivo tumor growth, Western blot for BAK/BAX, PI3K/AKT pathway analysis Nature medicine High 15502842
2007 Rab25 directly interacts with the β1 integrin cytoplasmic tail and promotes localization of integrin-recycling vesicles to pseudopodial tips, retaining a pool of cycling α5β1 integrin at the cell front. Rab25-driven tumor-cell invasion into 3D extracellular matrix is strongly dependent on fibronectin ligation by α5β1 and requires Rab25's capacity to interact with β1 integrin. Co-immunoprecipitation (direct interaction), live-cell imaging of vesicle localization, 3D invasion assays on fibronectin matrices, domain-interaction mutants Developmental cell High 17925226
2010 Rab25-deficient mice crossed onto ApcMin/+ background showed a 4-fold increase in intestinal polyps and 2-fold increase in colonic tumors compared to parental ApcMin/+ mice, establishing Rab25 as a tumor suppressor in intestinal neoplasia. Rab25-deficient mice also showed decreased β1 integrin staining in lateral membranes of villus cells. Similarly, Rab25-deficient mice crossed with Smad3+/- mice showed markedly increased colonic tumor formation. Rab25 knockout mice, genetic epistasis (ApcMin/+, Smad3+/- crosses), immunohistochemistry for β1 integrin, tumor counting The Journal of clinical investigation High 20197623
2011 Rab25 permits sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells, which colocalizes with active α5β1 in late endosomes/lysosomes and is necessary for cell rear release during migration. Photoactivation microscopy, biochemical fractionation, CLIC3 knockdown/overexpression, 3D invasion assays, organotypic cultures, Src signaling assays Developmental cell High 22197222
2011 Overexpression of Rab25 in non-transformed rat intestinal epithelial (RIE) cells caused morphological transformation, growth in soft agar, and tumor formation in nude mice. This transformation was reversed by inhibitors of microtubule polymerization but not by H-Ras(V12)-induced transformation, establishing microtubule-dependent trafficking as the mechanism of Rab25-driven transformation. Stable overexpression in RIE cells, soft agar assays, nude mouse tumorigenesis, microtubule inhibitor treatment, comparison with H-Ras(V12) transformation Cytoskeleton (Hoboken, N.J.) Medium 21246754
2012 RAB25 enhanced cancer cell survival during nutrient stress by binding and activating AKT, leading to increased glucose uptake, improved cellular bioenergetics, and unexpected accumulation of glycogen in epithelial cancer cells. AKT-dependent increases in glucose uptake and glycogen storage maintained ATP levels during bioenergetic stress. RAB25 overexpression/knockdown, AKT binding assays, glucose uptake assays, ATP/glycogen quantification, extracellular flux analysis, apoptosis assays under nutrient stress EMBO molecular medicine Medium 22253197
2012 Grhl2 transcriptionally upregulates Rab25 as one of its targets. Rab25 increases claudin-4 protein levels and enhances its localization to tight junctions, contributing to epithelial lumen formation and cyst expansion in 3D cultures. Grhl2 cDNA transfection, 3D cyst cultures, claudin localization by immunofluorescence, rescue/overexpression experiments Molecular biology of the cell Medium 22696678
2012 Rab25 acts as a tumor suppressor in esophageal squamous cell carcinoma (ESCC); functional studies showed Rab25 re-expression suppresses invasion and angiogenesis through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway. Downregulation of Rab25 in ESCC was associated with promoter hypermethylation. Lentiviral overexpression and suppression, invasion assays, angiogenesis assays, Western blot for FAK-Raf-MEK1/2-ERK pathway, bisulfite sequencing and demethylation treatment Cancer research Medium 22991305
2013 Crystal structure of Rab25 in complex with the C-terminal region of FIP2 was determined. Rab25 associates with FIP2 and recruits this effector to endosomal membranes. The structure reveals a heterotetrameric Rab25-(FIP2)2-Rab25 complex. FIP2 binds Rab25 with approximately 3-fold weaker affinity than Rab11a, with reduced enthalpy attributable to differences in switch 1 and switch 2 conformations. Crystal structure determination, isothermal titration calorimetry (ITC), co-localization by immunofluorescence, thermodynamic analysis Biochimica et biophysica acta High 24056041
2013 Rab25 directly associates with α5β1 integrins (colocalization and direct association shown) and controls integrin expression in polarized Caco2-BBE cells. Rab25 knockdown decreased α2-, α5-, and β1-integrin expression and upregulated claudin-1 expression, increased transepithelial resistance, and increased invasive behavior. Rab25 loss also decreased the transcription factor ETV4, and ETV4 overexpression in Rab25-knockdown cells reversed losses of α5β1-integrin. Stable shRNA knockdown, rescue by rabbit Rab25 re-expression, Co-IP/colocalization for direct association, gene expression arrays, transepithelial resistance measurement, invasion assays, ETV4 overexpression epistasis Molecular biology of the cell High 23345591
2013 Rab25 mediates secretion of osteoprotegerin (OPG), both at the transcription and secretion level. RAB25 expression increased OPG mRNA expression and secretion from ovarian and breast cancer cell lines, protecting cells from TRAIL-induced cell death. Rab25 cooperates with EGFR-mediated MAPK signaling to increase OPG production and release. Rab25 overexpression/siRNA knockdown, OPG ELISA, mRNA quantification, cell death assays, pharmacogenetic pathway inhibition Journal of genetic syndromes & gene therapy Medium 25520884
2013 Rab25 affects the organization of F-actin at the cell surface in head and neck squamous cell carcinoma (HNSCC). Re-expression of Rab25 in a metastatic HNSCC cell line blocked invasion in 3D collagen matrix and blocked metastasis to cervical lymph nodes in a mouse oral cancer model. Rab25 re-expression, intravital microscopy, 3D invasion assay, mouse model of oral cancer with lymph node metastasis quantification, F-actin staining Clinical cancer research Medium 23340300
2016 Rab25 regulates HIF-1α protein expression in an oxygen-independent manner in cancer cells, requiring de novo protein synthesis through the Erbb2/ERK1/2 and p70S6K/mTOR pathways (not transcriptional upregulation). Rab25 expression induced HIF-1 transcriptional activity, increased cisplatin resistance, and conferred intraperitoneal growth in vivo. Targeting HIF-1β re-sensitized Rab25-expressing cells to cisplatin. HIF-1α protein/mRNA analysis, pathway inhibitors (Erbb2/ERK1/2, mTOR), HIF-1β siRNA knockdown, in vivo peritoneal carcinomatosis model, MTT assays Oncotarget Medium 26967059
2016 Rab25 promotes turnover of lipid droplets in hepatic stellate cells (HSCs) through ROS-dependent mechanisms. HSC activation triggers Rab25 overexpression, and Rab25 promotes combination with PI3KCIII to direct autophagy to recognize and degrade lipid droplets. Rab25 siRNA blocked autophagy-mediated lipid droplet disappearance; ROS scavenging disrupted Rab25-autophagy interaction. Rab25 siRNA knockdown, Atg5 siRNA, autophagosome assays, Co-IP of Rab25 and PI3KCIII, antioxidant treatment, lipid droplet quantification Redox biology Medium 28038427
2016 Rab25 controls surface expression of CaV1.2 calcium channels in cerebral artery smooth muscle cells. Rab25 localizes in close spatial proximity to CaV1.2 (by immunoFRET); Rab25 knockdown reduced CaV1.2 surface and intracellular abundance, reduced whole-cell CaV1.2 current density, and inhibited pressure- and depolarization-induced vasoconstriction. CaV1.2 degradation upon Rab25 knockdown involved both lysosomal and proteasomal pathways. Immunofluorescence FRET (immunoFRET), siRNA knockdown, arterial biotinylation surface expression assay, patch-clamp electrophysiology, pressure myography American journal of physiology. Cell physiology High 27076616
2017 Stapled peptides derived from the RAB-binding FIP-family protein (RFP14) target RAB25 and inhibit RAB25:FIP complex formation in cells. Treatment with RFP14 inhibits migration and proliferation in a RAB25-dependent manner in pro-oncogenic contexts, and augments these phenotypes in tumor suppressive contexts, validating context-specific RAB25 oncogenic phenotypes. All-hydrocarbon stapled peptides, cell permeability assays, binding affinity measurements, RAB25:FIP complex inhibition, migration/proliferation assays, transcriptional profiling Nature communications High 28939823
2018 ZEB2 transcriptionally represses RAB25 by binding specifically to E-box sequences on the RAB25 promoter. ZEB2 binding is associated with local increases in DNA methylation (requiring DNMTs) and histone deacetylation (H3K9Ac) depending on SIRT1 activity. RAB25 contributes to partial suppression of ZEB2-mediated cell migration. Conditional ZEB2 expression, ChIP for ZEB2 at RAB25 promoter E-boxes, bisulfite sequencing for DNA methylation, H3K9Ac ChIP, SIRT1 inhibition, DNMT inhibition, migration assays Epigenetics & chromatin Medium 30445998
2018 Rab25 increases β1 integrin levels and subsequent EGFR activation, upregulating VEGF-A expression and leading to increased Snail expression, EMT, and cancer cell invasiveness. Snail mediates Rab25-induced invasiveness through fascin expression. Ectopic Rab25 expression promotes metastasis of ovarian cancer cells to the lung in vivo. Rab25 overexpression, Western blot for pathway components (β1 integrin, EGFR, VEGF-A, Snail, fascin), Snail knockdown epistasis, in vivo lung metastasis model Experimental & molecular medicine Medium 29371698
2019 Rab25 interacts with β1 integrin (shown by Co-IP) and promotes trafficking of β1 integrin to the cytoplasmic membrane. Membrane-localized β1 integrin induces AKT phosphorylation and subsequently activates the Wnt/β-catenin signaling pathway, promoting cell proliferation and mediating erlotinib resistance in NSCLC. Co-immunoprecipitation, Western blot, cell fractionation, lentiviral Rab25 knockin/knockout, cell proliferation and apoptosis assays, in vivo xenograft Cell proliferation Medium 30848009
2019 Loss of Rab25 promotes skin squamous cell carcinoma (SCC) development through dysregulation of integrin β1, β4, and α6 trafficking and expression. Rab25 deficiency caused impairment of integrin recycling, and Rab25 knockout mice showed accelerated tumor generation and malignant transformation in a two-stage skin carcinogenesis model. Rab25 knockout mice, two-stage skin carcinogenesis model, Rab25-deficient keratinocyte xenografts, integrin trafficking assays, immunohistochemistry The Journal of pathology Medium 31144312
2020 Rab25 interacts with EGFR (Co-IP) to enhance EGFR recycling to the cell surface and decrease EGFR degradation in the cytoplasm. This promotes hyperactive EGFR signaling and tumor radioresistance. Inhibition of Rab25 showed synergized radiosensitivity. Co-immunoprecipitation for Rab25-EGFR interaction, surface EGFR quantification, EGFR recycling/degradation assays, radiosensitivity assays iScience Medium 32252020
2020 RAB25 suppresses chemotherapy-induced mitochondrial apoptosis in ovarian cancer cells upstream of mitochondrial outer membrane permeabilization, either by increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. BAX expression negatively correlates with RAB25 expression. BH3 profiling confirmed RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by RNAi or stapled peptide RFP14 sensitizes cells to chemotherapy. RAB25 siRNA knockdown, RFP14 stapled peptide inhibition, BH3 profiling, Western blot for BCL-2 family members, chemotherapy sensitivity assays Apoptosis Medium 32901335
2021 Rab25 localizes near cytokinetic midbodies in zebrafish gastrula epithelium and coordinates cytokinetic bridge abscission through endomembrane trafficking. Loss of Rab25a and Rab25b caused persistent apical cytokinetic bridges, anisotropic cell morphologies, reduced contractile actomyosin networks, slowed cell rearrangements, and altered viscoelastic tissue responses, all contributing to delayed epiboly. Maternal-zygotic Rab25a and Rab25b mutant zebrafish, live imaging, immunofluorescence for midbody localization, actomyosin quantification, tissue mechanics measurement eLife High 33755014
2021 Rab25 participates in regulation of aerobic glycolysis via PKM2 in gastric adenocarcinoma. Rab25 protein and PKM2 protein co-localize on the cell membrane and directly bind each other. Rab25 is a positive regulator of PKM2 and promotes phosphorylation of PKM2 at Y105. Co-immunoprecipitation, immunofluorescence colocalization, lentiviral Rab25 silencing/overexpression, pyruvate/lactate quantification, PKM2 phosphorylation by Western blot Translational cancer research Medium 35116410
2022 RAB25 coordinates keratohyalin granule (KHG) maturation by regulating actin dynamics in keratinocytes. RAB25-deficient mice showed decreased KHG production and abnormal KHG processing. In HaCaT cells, RAB25 co-expressed with filaggrin-containing KHG, and RAB25 silencing impaired KHG formation through abnormal actin dynamics. Rab25 knockout mice, oxazolone AD model, RAB25 siRNA in HaCaT cells, immunofluorescence, KHG quantification, actin dynamics assays Allergy Medium 36383036
2023 Rab25 induces claudin-7 expression through protein stabilization in colon cancer cells. Claudin-7 inactivates EGFR and reduces Snail expression; silencing claudin-7 reversed the tumor-suppressive role of Rab25. Rab25 also inactivated EGFR and increased E-cadherin expression. Rab25 overexpression, claudin-7 knockdown epistasis, 3D Matrigel invasion assay, modified Boyden chamber, Western blot for EGFR/E-cadherin/Snail, claudin-7 protein stability assay Oncology reports Medium 38131227
2025 RAB25 promotes ADAMTS5 expression through activation of the NF-κB signaling pathway in ovarian cancer cells. ADAMTS5 is necessary and sufficient to stimulate ovarian cancer cell migration through fibroblast-secreted matrices, and selective ADAMTS5 inhibition prevented ovarian cancer spheroid invasion in 3D systems. Rab25 overexpression/knockdown, NF-κB pathway inhibition and reporter assay, ADAMTS5 knockdown/overexpression, 3D invasion spheroid assays The FEBS journal Medium 40164572
2025 RAB25 interacts with GCN1 (confirmed by mass spectrometry and Co-IP), and this interaction inhibits K33-ubiquitination-mediated degradation of GCN1, promoting GCN2 phosphorylation and subsequently activating ATF4-mediated ER stress in hepatocytes during alcohol-associated liver disease. RAB25 specifically accumulates on the ER in ALD. Mass spectrometry, Co-immunoprecipitation, K33-ubiquitination assays, GCN2 phosphorylation, ATF4/ER stress markers, RAB25 knockdown in vitro and in vivo Clinical and molecular hepatology Medium 40916695
2025 RAB25 loss in gastric epithelial cells facilitates TGF-α secretion, which promotes upregulation of EGFR signaling in the pit region and drives pit cell lineage commitment. Long-term alteration of TGF-α secretion in Rab25 KO mice caused gastric lesions with massive foveolar hyperplasia, which was ameliorated by TGF-α neutralization. Rab25 KO mice, mouse primary cell culture, single-cell RNA sequencing, TGF-α neutralization in vivo, EGFR pathway analysis by Western blot Cell death & disease Medium 41365858
2024 Magnetogenetic positioning of Rab25 vesicles to the cell periphery directly drives formation of F-actin protrusions. Endogenous Rab25 vesicles coordinate positioning of actin regulator FMNL1 and integrin β1 with activation of Rho GTPases at the plasma membrane to generate and maintain F-actin rich filopodial protrusions and promote cancer cell invasive migration in 3D matrix. Magnetogenetic approach for direct Rab25 vesicle positioning, live-cell imaging, F-actin quantification, FMNL1 and integrin β1 colocalization, Rho GTPase biosensor bioRxivpreprint Medium
2010 The RAB25 promoter contains a CRE element (-67/-58) that binds CREB within the core promoter region. PKA activator forskolin enhances open chromatin accessibility at this CRE, facilitating CREB phosphorylation, recruitment of co-factors CBP and Brg1, histone modification, and heightened RAB25 expression. PCR-based chromatin accessibility assay, ChIP, EMSA, deletion constructs with luciferase reporter, forskolin treatment The international journal of biochemistry & cell biology Medium 21075212
2015 CCN3 overexpression in cortical neurons inhibits axonal outgrowth, with RAB25 identified as a downstream effector by transcriptomic analysis. In vivo ectopic expression of RAB25 or dominant-negative RAB25-T26N demonstrated that GTPase activity of RAB25 is required for CCN3-mediated inhibition of neuronal outgrowth. In vivo cortical electroporation, transcriptomic analysis, RAB25 and dominant-negative RAB25-T26N overexpression, axonal outgrowth quantification Biochemical and biophysical research communications Low 25871796

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 264 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 99 22991305
2016 Autophagy regulates turnover of lipid droplets via ROS-dependent Rab25 activation in hepatic stellate cell. Redox biology 92 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
2021 The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium. eLife 15 33755014
2018 ZEB2 stably represses RAB25 expression through epigenetic regulation by SIRT1 and DNMTs during epithelial-to-mesenchymal transition. Epigenetics & chromatin 15 30445998
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
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
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
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 4 30232331
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
2025 RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression. Clinical and molecular hepatology 1 40916695
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 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

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