Affinage

RHOC

Rho-related GTP-binding protein RhoC · UniProt P08134

Length
193 aa
Mass
22.0 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 43 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

RhoC is a membrane-associated small GTPase that regulates actin cytoskeleton dynamics and is the principal Rho isoform driving tumor cell motility, invasion, and metastasis (PMID:2501082, PMID:10952316, PMID:16107613). Genetic ablation establishes that RhoC is dispensable for embryogenesis and tumor initiation but specifically required for metastasis, acting on tumor cell motility and metastatic cell survival (PMID:16107613). Biochemically RhoC is distinguished from RhoA by higher intrinsic GTP-binding affinity, faster exchange kinetics, and predominantly membrane localization, and its biological activity depends on geranylgeranylation for proper subcellular targeting (PMID:14578459, PMID:19642867). RhoC cycling is governed by isoform-selective regulators: SmgGDS and p190RhoGEF activate it while p190RhoGAP and ARHGAP21 inactivate it, and a structural determinant (Ile43) excludes activation by the GEF XPLN (PMID:12221096, PMID:21474314, PMID:21242305, PMID:23200924). Live-biosensor imaging shows RhoC activity is spatially confined to the rim surrounding invadopodia by reciprocal localization of p190RhoGEF and p190RhoGAP, restricting cofilin-mediated actin barbed-end generation to the invadopodium core and directing protrusion (PMID:21474314, PMID:24224016, PMID:23704350). Downstream, RhoC signals through the RhoC-selective formin effectors FMNL2 and FMNL3, through ROCK1/ROCK2, and through IQGAP1 to remodel actin, control migratory polarity, and drive invasion and proliferation (PMID:20101212, PMID:21576392, PMID:21537845, PMID:23145020, PMID:30228782). Upstream, RhoC is activated or stabilized by PKCε- and Akt1-mediated phosphorylation, by p38γ-controlled ubiquitination, and by direct binding of BCAT1 and branched-chain α-keto acids, while RNF180-mediated ubiquitination targets it for degradation (PMID:17018591, PMID:21862636, PMID:22896661, PMID:33082325, PMID:37337119). Beyond cancer cell-autonomous invasion, RhoC promotes angiogenic factor secretion and MMP induction, endothelial barrier and proliferation homeostasis, cancer stem cell maintenance via IL-6/STAT3, and radioresistance via a ROCK2-DNA repair axis (PMID:11191108, PMID:14871999, PMID:26136364, PMID:31488179, PMID:24533098).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    Established that a Rho protein controls actin microfilament organization, the foundational activity later attributed to RhoC-driven cell shape change.

    Evidence In vitro C3 exoenzyme ADP-ribosylation of bacterially expressed RhoC plus microfilament/morphology readout in Vero cells

    PMID:2501082

    Open questions at the time
    • C3 does not distinguish RhoC from other Rho isoforms
    • no isoform-specific effectors identified
    • no link to invasion or metastasis yet
  2. 2000 High

    Defined RhoC as a functional driver of tumor cell invasion and metastasis rather than a passive marker, and linked it to angiogenic factor production.

    Evidence Gain- and dominant-negative loss-of-function in melanoma and mammary epithelial cells with in vivo metastasis assays and ELISA for angiogenic factors

    PMID:10952316 PMID:11191108

    Open questions at the time
    • dominant-negative Rho is not RhoC-selective
    • direct effectors mediating invasion unidentified
    • mechanism linking RhoC to angiogenic secretion unresolved
  3. 2002 High

    Showed that GEF activation of RhoC is isoform-selective and identified the structural determinant (Ile43) governing GEF discrimination among Rho isoforms.

    Evidence In vitro nucleotide exchange assays and site-directed mutagenesis comparing XPLN action on RhoA/B/C

    PMID:12221096

    Open questions at the time
    • did not identify the physiological RhoC GEF
    • structural basis tested for one GEF only
  4. 2003 Medium

    Demonstrated that RhoC requires geranylgeranylation for membrane localization and biological activity, defining a druggable post-translational dependency.

    Evidence Atorvastatin (HMG-CoA reductase) inhibition with subcellular fractionation, Rho activity assays, and in vivo metastasis of RhoC-overexpressing cells

    PMID:14578459

    Open questions at the time
    • statin effects not RhoC-specific
    • prenylation enzymes not directly perturbed
    • in vivo specificity for RhoC over RhoA limited
  5. 2004 Medium

    Distinguished RhoC from RhoA functionally, showing RhoC selectively promotes invasion (not proliferation) and that RhoA/RhoC and Rac1 are reciprocally balanced.

    Evidence Selective retroviral RNAi of RhoA vs RhoC with invasion assays and Rho/Rac activity measurements; orthotopic lung model linking RhoC to MMP-2

    PMID:14871999 PMID:15574779

    Open questions at the time
    • molecular basis of RhoA/RhoC antagonism unresolved at this stage
    • effector mediating invasion not identified
    • single cell-line systems
  6. 2005 High

    Provided definitive in vivo genetics establishing RhoC as required for metastasis but dispensable for development and tumor initiation.

    Evidence RhoC knockout mouse with tumor induction, motility, survival, and metastasis quantification

    PMID:16107613

    Open questions at the time
    • does not define the effector pathway responsible in vivo
    • potential compensation by RhoA not fully excluded
  7. 2006 Medium

    Dissected the downstream signaling branches, separating RhoC-driven invasion (ROCK-independent PI3K/Akt and FAK/MAPK) from random motility and from anchorage-independent growth.

    Evidence Pharmacological pathway dissection and dominant-negative/C3 inhibition in melanoma and prostate cancer cells with invasion/motility readouts

    PMID:16314838 PMID:16470169

    Open questions at the time
    • pharmacological inhibitors lack isoform selectivity
    • direct RhoC-effector contacts not demonstrated
  8. 2010 High

    Identified RhoC-selective formin effectors (FMNL2, FMNL3) and isoform-specific roles in integrin regulation and endothelial homeostasis, explaining RhoC's distinct cytoskeletal output.

    Evidence siRNA formin screen with selective active-GTPase pulldowns and 3D invasion epistasis; isoform-selective RNAi for integrin surface expression; HUVEC and zebrafish endothelial assays

    PMID:20101212 PMID:20503409 PMID:26136364

    Open questions at the time
    • structural basis of FMNL2/3 selectivity for RhoC not resolved
    • endothelial mechanisms from single lab
  9. 2011 High

    Resolved the spatial control of RhoC at invadopodia and defined its dedicated GEF/GAP pair, plus ROCK1/2 and FMNL3 partitioning of migratory polarity.

    Evidence RhoC FLARE biosensor live imaging with p190RhoGEF/p190RhoGAP localization and cofilin phosphorylation readouts; reciprocal RNAi with FMNL3/ROCK epistasis

    PMID:21474314 PMID:21576392

    Open questions at the time
    • recruitment mechanism positioning p190RhoGEF vs p190RhoGAP unresolved
    • biosensor used in limited cell types
  10. 2011 Medium

    Established additional isoform-selective regulators and effectors—SmgGDS as a RhoA/RhoC-specific activator, PKN3 and IQGAP1 as preferential RhoC partners, and PKCε/p38γ/RhoGDIα as upstream controllers of RhoC activity and stability.

    Evidence In vitro exchange assays across a large GTPase panel with mutagenesis; Co-IP and in vitro kinase assays; RNAi/rescue epistasis and ubiquitination assays

    PMID:17018591 PMID:21242305 PMID:21537845 PMID:21757538 PMID:21862636 PMID:22217540

    Open questions at the time
    • several interactions rest on single Co-IP studies
    • direct PKCε phosphorylation of RhoC inferred not proven
    • in vivo relevance of each axis variable
  11. 2012 High

    Demonstrated direct Akt1 phosphorylation of RhoC as essential for inflammatory breast cancer invasion, and confirmed IQGAP1 as a proliferative effector, linking specific kinase inputs to RhoC output.

    Evidence In vitro Akt1 kinase assay with phospho-specific detection and isoform-selective siRNA rescue; Co-IP and proliferation assays for IQGAP1

    PMID:22896661 PMID:23145020

    Open questions at the time
    • phosphosite consequences on GTPase cycle not structurally defined
    • clinical correlation from single cohort
  12. 2013 Medium

    Quantified RhoC biochemical distinctiveness and effector binding (PRK/PKN affinities, ARHGAP21 GAP activity) and refined spatiotemporal models of RhoC vs RhoA during protrusion.

    Evidence In vitro binding/affinity assays, GAP activity assays, and FRET biosensor live imaging with computational analysis

    PMID:23200924 PMID:23704350 PMID:24128008 PMID:24224016

    Open questions at the time
    • functional consequence of PRK affinity differences in cells untested
    • GAP studies from single lab
  13. 2017 Medium

    Placed RhoC within transcriptional/microenvironmental regulatory networks, with HIF-3α, Notch1, p53, and miRNAs (miR-10b, miR-493) controlling RhoC expression or RhoC-ROCK1 signaling.

    Evidence Transcriptional reporter/ChIP assays, miRNA 3'UTR luciferase and Co-IP, and pharmacological/genetic interventions with invasion readouts

    PMID:19953094 PMID:20843787 PMID:21079653 PMID:22057916 PMID:28928287

    Open questions at the time
    • several transcriptional links inferred from reporter assays
    • context-dependence across tumor types not reconciled
  14. 2020 High

    Defined antagonistic and degradative control of RhoC—the RhoD-PAK6 axis suppressing RhoC-dependent contraction, RNF180 driving RhoC degradation, and ROCK-mediated endothelial transmigration—expanding the regulatory and effector network.

    Evidence Genetic epistasis in viral infection and normal cells, Co-IP plus ubiquitination proteomics, and RNAi cancer-endothelial interaction assays

    PMID:25677806 PMID:28486133 PMID:33082325

    Open questions at the time
    • RNF180 link rests on single-lab Co-IP/proteomics
    • physiological setting for RhoD-PAK6 antagonism beyond viral context limited
  15. 2023 High

    Connected RhoC to metabolism, showing BCAT1 and branched-chain α-keto acids directly bind and activate RhoC to promote motility, defining a metabolite-driven activation mode.

    Evidence Co-IP of BCAT1-RhoC, in vitro BCKA-RhoC binding, activity assays, BCAT1E61A rescue, and in vivo peritoneal metastasis model

    PMID:37337119

    Open questions at the time
    • binding site of BCKA on RhoC not structurally mapped
    • single-lab in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many isoform-selective regulators and effectors are integrated spatiotemporally in vivo, and the structural basis distinguishing RhoC from RhoA at the effector/regulator interface, remain unresolved.
  • no high-resolution structure of RhoC with its selective GEFs/GAPs/effectors
  • lack of in vivo causal ordering of the upstream kinase/metabolite/ubiquitin inputs
  • redundancy and compensation with RhoA not fully separated genetically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
BCAT1FMNL2FMNL3IQGAP1PKN3ROCK1ROCK2SMGGDS

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 RhoC protein is ADP-ribosylated by Clostridium botulinum exoenzyme C3, and C3 treatment of Vero cells causes disappearance of actin microfilaments and actinomorphic shape changes, establishing that a rho protein (RhoC) regulates actin microfilament assembly. Bacterial expression of human rhoC gene product, in vitro ADP-ribosylation assay, cell treatment with C3 exoenzyme and morphological analysis The EMBO journal High 2501082
2000 Overexpression of RhoC in melanoma cells enhances metastasis and invasion, while dominant-negative Rho inhibits metastasis, establishing RhoC as a functional driver of tumor cell invasion in vivo. In vivo selection of metastatic melanoma cells, DNA microarray gene expression analysis, overexpression and dominant-negative constructs, in vivo metastasis assays Nature High 10952316
2000 RhoC GTPase overexpression in human mammary epithelial cells increases production of angiogenic factors (VEGF, bFGF, IL-6, IL-8); inhibition of RhoC with C3 exotransferase decreases angiogenic factor production, directly linking RhoC activity to angiogenic signaling. Stable transfection of RhoC in HME cells, ELISA measurement of conditioned media, C3 exotransferase inhibition Neoplasia (New York, N.Y.) High 11191108
2002 XPLN, a guanine nucleotide exchange factor, stimulates GDP/GTP exchange on RhoA and RhoB but NOT RhoC in vitro; the inability to activate RhoC is determined by isoleucine 43 in RhoC (a position occupied by valine in RhoA and RhoB), establishing a structural basis for GEF selectivity among Rho isoforms. In vitro nucleotide exchange assays, preferential binding assays, site-specific mutagenesis (Ile43 in RhoC), cellular stress fiber/focal adhesion assays The Journal of biological chemistry High 12221096
2002 Activation of the MAPK pathway downstream of RhoC GTPase is responsible for motility, invasion, and production of angiogenic factors in inflammatory breast cancer cells, while PI3K pathway activation drives anchorage-independent growth. Pharmacological inhibitors of MAPK and PI3K pathways in HME-RhoC transfectants and SUM149 IBC cells; motility, invasion, and angiogenesis assays Clinical & experimental metastasis Medium 12090470
2003 Atorvastatin prevents geranylgeranylation (isoprenylation) of RhoC, inhibiting its subcellular localization and activity, and blocks melanoma cell invasion in vitro and in vivo metastasis of RhoC-overexpressing cells, establishing that RhoC biological activity depends on posttranslational geranylgeranylation. HMG-CoA reductase inhibitor treatment, subcellular fractionation and Rho activity assays, in vitro invasion assays, in vivo melanoma metastasis model Molecular cancer therapeutics Medium 14578459
2004 RhoC stimulates invasion but not proliferation in invasive breast carcinoma (SUM-159) cells; RhoA impedes invasion; a compensatory relationship exists between RhoA and RhoC expression/activation levels, and RhoC depletion inversely affects Rac1 activation. Stable retroviral RNAi knockdown of RhoA or RhoC, invasion assays, Rho and Rac1 activity measurements Cancer research Medium 15574779
2004 In orthotopic lung cancer mouse model, RhoC overexpression enhances metastasis and increases MMP-2 activity, while dominant-negative Rho suppresses both, without affecting primary tumor growth; establishing RhoC as a promoter of metastasis through MMP upregulation. Retroviral transduction of RhoC or dominant-negative Rho into murine lung cancer cells, orthotopic intrapulmonary inoculation, RT-PCR and gelatin zymography for MMPs Clinical cancer research Medium 14871999
2004 Loss of WISP3 in HME cells increases RhoC mRNA and protein levels, while restoration of WISP3 in IBC cells decreases RhoC protein, indicating that WISP3 modulates RhoC expression and the two genes cooperate in the IBC phenotype. Antisense inhibition of WISP3, RT-PCR and Western blot for RhoC, VEGF ELISA, soft agar growth assays Breast cancer research : BCR Medium 14696649
2005 RhoC-deficient mice (RhoC knockout) are viable and fertile; loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival, leading to drastic inhibition of metastasis, establishing RhoC as specifically required for metastasis but dispensable for embryogenesis and tumor initiation. RhoC knockout mouse generation, tumor induction models, cell motility and survival assays, metastasis quantification Genes & development High 16107613
2006 RhoC is required for invasion but not random motility in PC-3 prostate cancer cells; inhibition of RhoC with C3 exotransferase or dominant-negative RhoC promotes IGF-I-stimulated random motility but decreases invasion and experimental metastasis, and causes alterations in focal adhesion protein distribution. C3 exotransferase pharmacological inhibition and dominant-negative RhoC overexpression, chemotaxis chamber assays, in vivo experimental metastasis, immunofluorescence of focal adhesion proteins Oncogene Medium 16314838
2006 PKCε knockdown in HNSCC cells reduces active and serine-phosphorylated RhoA and RhoC; constitutively active RhoC rescues invasion and partially rescues motility in PKCε-deficient cells, establishing RhoC as a downstream effector of PKCε, possibly through direct post-translational phosphorylation. siRNA knockdown of PKCε, constitutively active RhoC rescue experiments, invasion and motility assays, Western blot for phospho-RhoC/RhoA Cancer research Medium 17018591
2008 RhoC promotes prostate cancer metastasis via sequential activation of Pyk2, FAK, MAPK, and Akt, followed by upregulation of MMP2 and MMP9; inhibition of Pyk2 blocks RhoC-dependent activation of FAK, MAPK, and Akt and suppresses MMP activity. RhoC overexpression in prostate cancer cells, antibody array for signaling molecules, Pyk2 kinase inhibitor treatment, in vitro invasion/motility assays, in vivo metastasis model Cancer research Medium 18794150
2010 Formin-like 2 (FMNL2) is a specific effector of RhoC but not RhoA or RhoB; FMNL2 shows selective interaction with active RhoC, and RhoC regulates FMNL2 autoinhibition; suppression of FMNL2 inhibits RhoC-dependent but not RhoA-dependent rounded invasive cell migration. siRNA-based screen of all 15 human formins in 3D cell motility, selective pulldown with active GTPase forms, knockdown rescue experiments in cancer cell lines Oncogene High 20101212
2010 HA-induced CD44 interaction with c-Src kinase activates Twist, which drives miR-10b transcription; miR-10b suppresses HOXD10, leading to RhoA/RhoC upregulation and ROCK activation, resulting in breast tumor cell invasion. This pathway is abrogated by c-Src inhibition, Twist siRNA, or anti-miR-10b inhibitor. ChIP assays for Twist at miR-10b promoter, siRNA and inhibitor experiments, Western blot for RhoC/RhoA/ROK, invasion assays The Journal of biological chemistry Medium 20843787
2011 RhoC activity is spatially confined to areas surrounding invadopodia, regulated by p190RhoGEF (which localizes around invadopodia to activate RhoC) and p190RhoGAP (which localizes inside invadopodia to deactivate RhoC); RhoC activation surrounding invadopodia enhances cofilin phosphorylation outside the structure, restricting cofilin-mediated actin barbed end generation to within the invadopodium core. Live-cell imaging with fluorescent RhoC FLARE biosensor, immunofluorescence localization of p190RhoGEF and p190RhoGAP, cofilin phosphorylation assays Current biology : CB High 21474314
2011 RhoC depletion increases cell spreading and induces Rac1 activation around the cell periphery in broad lamellipodia, inhibiting directed migration and invasion; these effects are mediated by formin FMNL3, identified as a new effector of RhoC but not RhoA; RhoA acts through ROCK1/ROCK2 to regulate migratory polarity. RNAi knockdown of RhoA and RhoC, 2D and 3D migration/invasion assays, Rac1 activity measurements, FMNL3 knockdown rescue epistasis The Journal of cell biology High 21576392
2011 p38γ MAPK regulates RhoC expression by modulating RhoC ubiquitination; p38γ knockdown reduces RhoC protein levels and inhibits breast cancer cell motility and metastasis. p38γ knockdown, Western blot for RhoC, ubiquitination assay, motility assays, computational cell mechanics model, clinical specimen correlation Cancer research Medium 21862636
2011 PKN3 physically interacts preferentially with RhoC over other Rho GTPases; PKN3 catalytic activity is increased in the presence of Rho GTPases; the PKN3-RhoC complex is co-expressed in late-stage malignancies and contributes to tumor invasion and metastasis. Co-immunoprecipitation, in vitro kinase activity assay with Rho GTPases, orthotopic mouse tumor models with PKN3 knockdown Molecular oncology Medium 22217540
2011 SmgGDS exclusively activates RhoA and RhoC (not other tested GTPases) in vitro; this specificity is catalytic and requires the polybasic region of RhoA for activation; SmgGDS uses a distinct exchange mechanism from canonical GEFs. This specificity is retained in cells. In vitro nucleotide exchange assays on a large panel of purified GTPases, mutagenesis of SmgGDS and RhoA, preferential nucleotide-depleted state binding assay, cellular GEF activity assays The Journal of biological chemistry High 21242305
2011 RhoC and IQGAP1 bind to each other (co-immunoprecipitation); RhoC stimulates migration of gastric cancer cells through IQGAP1 as a downstream effector; knockdown of IQGAP1 blocks RhoC-induced migration stimulation. Co-immunoprecipitation, siRNA knockdown of RhoC and IQGAP1, constitutively active RhoC overexpression, transwell migration assay Molecular medicine reports Medium 21537845
2011 RhoGDIα-mediated balance between RhoA and RhoC controls invasive phenotype; RhoC silencing increases expression of tumor suppressor NAG-1 and reduces migration and anchorage-independent growth; this occurs indirectly through upregulation of RhoA via competition for RhoGDIα. siRNA knockdown of RhoC, RhoA, and RhoGDIα, RhoA mutant unable to bind RhoGDIα, gene expression profiling, migration and soft agar assays, in vivo tumor growth Molecular biology of the cell Medium 21757538
2012 Akt1 directly phosphorylates RhoC GTPase, and this phosphorylation is absolutely essential for IBC cell invasion; Akt3 (not Akt1) regulates IBC cell survival; PI3K/Akt1/RhoC pathway is specifically upregulated in IBC patients. In vitro Akt1 kinase assay with RhoC substrate, phospho-specific detection, siRNA knockdown of Akt isoforms, invasion assays, clinical IBC specimen analysis Molecular cancer research : MCR High 22896661
2012 RhoC and IQGAP1 bind each other; RhoC stimulates gastric cancer cell proliferation through IQGAP1 by increasing cyclin E and cyclin D1 levels; IQGAP1 knockdown blocks RhoC-induced proliferation but not vice versa, defining IQGAP1 as a downstream effector of RhoC in proliferation. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, constitutively active RhoC overexpression, MTT and BrdU proliferation assays, Western blot for cyclins PloS one Medium 23145020
2013 A RhoC FLARE biosensor revealed that RhoC activity is higher than RhoA in regions distal from the cell edge during protrusion; RhoC activation precedes RhoA activation distally before edge protrusion; p190RhoGEF and p190RhoGAP regulate actin barbed end distribution and protrusion directionality through RhoC activity balance. FRET-based RhoC FLARE biosensor live imaging, comparison with RhoA biosensor, computational analysis of spatio-temporal GTPase activity during protrusion/retraction and macropinocytosis PloS one / Journal of cell science High 23704350 24224016
2010 RhoC promotes vascular homeostasis in endothelial cells: it stimulates proliferation by stabilizing nuclear β-catenin (promoting cyclin D1 transcription); negatively regulates migration through MAPKs/MLC2 signaling; and decreases vascular permeability through downregulation of PLCγ-Ca2+-eNOS cascade. RhoC morpholino in zebrafish increases vascular permeability. HUVEC siRNA/overexpression experiments, Western blot for β-catenin/cyclin D1/MLC2/eNOS, permeability assays, zebrafish RhoC morpholino model Journal of cell science Medium 26136364
2006 RhoC promotes melanoma invasion through a PI3K/Akt pathway independent of ROCK signaling; RhoC overexpression increases phospho-Akt (Ser473); inhibition of PI3K or Akt (but not ROCK) decreases pAkt levels; both ROCK and PI3K/Akt pathways contribute independently to RhoC-driven invasion. Stable RhoC overexpression in melanoma cells, C3 transferase inhibition, PI3K/Akt/ROCK pharmacological inhibitors, Western blot for pAkt, invasion assays The Journal of investigative dermatology Medium 16470169
2010 RhoC (but not RhoA) modulates surface expression and colocalization of α2 and β1 integrins in MDA-MB-231 cells on collagen I, establishing a specific role for RhoC in cell-matrix adhesion through integrin regulation. Selective siRNA knockdown of RHOC vs RHOA, flow cytometry and immunofluorescence for integrin surface expression, collagen I and Matrigel invasion/adhesion assays Cancer Medium 20503409
2013 ARHGAP21 functions as a RhoGAP with enzymatic activity toward both RhoA and RhoC; its depletion in PC3 prostate cancer cells decreases proliferation and increases migration. In vitro GAP activity assay for RhoA and RhoC, siRNA knockdown in LNCaP and PC3 cells, proliferation and migration assays Biochimica et biophysica acta Medium 23200924
2009 RhoC has higher intrinsic GTP binding affinity, faster intrinsic and GEF-stimulated GDP/GTP exchange rates than RhoA; RhoC is predominantly localized in the membrane-containing fraction whereas RhoA is mainly cytoplasmic; these biochemical differences are not due to differential RhoGDI interaction and correlate with RhoC-specific enhancement of migration and invasion in pancreatic carcinoma cells. In vitro GTP/GDP binding and exchange assays, subcellular fractionation, RhoGDI interaction assays, serum-response factor reporter assays, migration and invasion assays Biological chemistry High 19642867
2013 Differential binding affinities of PRK isoforms (PRK1, PRK2, PRK3) for RhoA, RhoB, and RhoC were measured; RhoA and RhoC bind PRK1 HR1a domain with similar affinities; PRK2 and PRK3 domains bind all Rho isoforms less well than PRK1; establishing quantitative interaction parameters for RhoC-PRK signaling. In vitro binding/affinity assays using purified HR1 domain constructs and purified Rho GTPases, thermal stability analysis Biochemistry Medium 24128008
2010 p53 directly transcriptionally activates RhoC and LIMK2 expression in response to genotoxic agents; LIMK2 activation downstream of RhoC has a pro-survival function following DNA damage; LIMK inhibition sensitizes cells to radio- or chemotherapy. ChIP (implied by 'direct p53 target genes'), siRNA knockdown of LIMK2, pharmacological LIMK inhibition, genotoxic agent treatment, cell survival assays Cell research Medium 21079653
2011 Notch1 signaling regulates RhoC activity in cervical carcinoma; Notch1 inhibition with DAPT decreases RhoC activity; constitutively active RhoC rescues the phenotypic effects of Notch1 inactivation on invasion, migration, and anoikis resistance, placing RhoC as an effector of Notch1. Pharmacological Notch1 inhibition with DAPT, Rho activity assay (G-LISA), constitutively active RhoC rescue experiments, invasion/migration/anoikis assays British journal of cancer Medium 19953094
2012 miR-493 decreases RhoC 3'UTR luciferase activity and protein expression in bladder cancer cells, and decreases RhoC-ROCK1 binding, thereby reducing cell motility and migration. miR-493 transfection, 3'UTR luciferase reporter assay, Western blot for RhoC, co-immunoprecipitation for RhoC-ROCK1 interaction, migration assays Molecular cancer therapeutics Medium 22057916
2017 HIF-3α promotes pancreatic cancer invasion by transcriptionally activating the RhoC-ROCK1 signaling pathway under hypoxic and normoxic conditions; HIF-3α overexpression stimulates F-actin polymerization. HIF-3α knockdown and overexpression, ChIP/transcriptional reporter assays for RhoC promoter (implied), invasion/migration assays, F-actin staining, in vivo xenograft Molecular cancer research : MCR Medium 28928287
2017 RhoD recruits PAK6 to the plasma membrane to antagonize RhoC signaling and suppress RhoC-dependent cell contraction and blebbing; vaccinia virus F11 protein inhibits RhoD, thereby relieving PAK6 suppression of RhoC and enabling ROCK-mediated cell contraction specifically through RhoC (not RhoA). Vaccinia infection model, RhoC/RhoD/PAK6 knockdowns, localization studies, ROCK inhibition, genetic epistasis with constitutively active/dominant-negative constructs Developmental cell High 28486133
2015 RhoC depletion by RNAi reduces PC3 prostate cancer cell adhesion to endothelial cells, intercalation between endothelial cells, and transendothelial migration in vitro; ROCK1 and ROCK2 depletion similarly decreases cancer-endothelial interactions; RhoC depletion reduces early lung retention and experimental metastasis in vivo. RNAi depletion of RhoC, ROCK1, ROCK2; adhesion, intercalation, transendothelial migration assays; in vivo lung retention and metastasis experiments Molecular oncology Medium 25677806
2019 RhoC promotes radioresistance in cervical cancer via ROCK2, which interacts with DNA repair pathway proteins (pH2Ax, MRE11, RAD50); ROCK2 inhibition reduces expression of pH2Ax and MRN complex proteins, and abolishes RhoC-conferred radioresistance, establishing RhoC-ROCK2 as a regulator of the DNA repair machinery. RhoC overexpression/siRNA, ROCK2 inhibition/siRNA, immunofluorescence for DNA repair markers, transcriptomic profiling, radiation survival assays, clinical sample analysis Journal of experimental & clinical cancer research : CR Medium 31488179
2020 RNF180 E3 ubiquitin ligase directly binds RhoC and promotes its ubiquitination and proteasomal degradation; RhoC knockdown reduces STAT3 phosphorylation in gastric cancer cells, placing RhoC upstream of STAT3 activation. Co-immunoprecipitation for RNF180-RhoC interaction, ubiquitin label-free proteomics, RhoC shRNA knockdown, Western blot for STAT3 phosphorylation Cell death & disease Medium 33082325
2023 BCAT1 directly interacts with RhoC, elevating RhoC activity; branched-chain α-keto acids (BCKA), derived from BCAA catabolism, directly bind RhoC and promote its activity; BCAT1E61A mutation confers higher enzymatic activity and boosts RhoC-dependent cell motility; candesartan inhibits BCAT1E61A activity and represses RhoC activity. Co-immunoprecipitation of BCAT1-RhoC, in vitro BCKA-RhoC binding assay, RhoC activity assays, BCAT1 knockout/rescue with BCAT1E61A, in vitro motility assays, in vivo peritoneal metastasis model Nature metabolism High 37337119
2019 FMNL3 interacts directly with RhoC (demonstrated by Co-IP, immunofluorescence co-localization, and GST pull-down), acts as an effector of RhoC to activate the FAK/p-MAPK/p-AKT signaling pathway, and regulates RhoC-dependent remodeling of actin-based protrusions (filopodia and lamellipodia) to promote colorectal cancer cell invasion. Co-immunoprecipitation, immunofluorescence co-localization, GST pull-down assay, FAK/MAPK/AKT Western blot, pharmacological inhibitors (TAE226, U0126, LY294002), invasion/migration assays World journal of gastroenterology Medium 30228782
2015 RhoC regulates cancer stem cell (CSC) formation in HNSCC by promoting IL-6 secretion, which rescues STAT3 phosphorylation; RhoC knockdown decreases ALDH, CD44, and stem cell transcription factors (Nanog, Oct3/4, Sox2) and reduces STAT3 phosphorylation; IL-6 stimulation rescues STAT3 phosphorylation in RhoC knockdown lines. shRNA knockdown of RhoC, ALDH/CD44 flow cytometry, tumorsphere formation, IL-6 ELISA, Western blot for STAT3 phosphorylation, STAT3 overexpression rescue PloS one Medium 24533098
2015 Caveolin-1 overexpression mediates IBC cell invasion through activation of Akt1, which phosphorylates RhoC GTPase; caveolin-1 siRNA knockdown decreases Akt1 activation and thereby decreases RhoC phosphorylation and IBC cell invasion. caveolin-1 siRNA and scaffolding domain inhibition, Western blot for Akt1 activation and RhoC phosphorylation, invasion assays Journal of cellular biochemistry Medium 25559359

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Genomic analysis of metastasis reveals an essential role for RhoC. Nature 1225 10952316
1989 The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. The EMBO journal 501 2501082
2004 Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Experimental cell research 389 15501444
1998 Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. British journal of cancer 246 9459160
2009 MicroRNA-10b is overexpressed in malignant glioma and associated with tumor invasive factors, uPAR and RhoC. International journal of cancer 244 19536818
2005 RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes & development 243 16107613
2011 RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. The Journal of cell biology 224 21576392
2005 Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo. Molecular therapy : the journal of the American Society of Gene Therapy 210 15668138
2003 Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Laboratory investigation; a journal of technical methods and pathology 192 12808121
2010 Hyaluronan-CD44 interaction promotes c-Src-mediated twist signaling, microRNA-10b expression, and RhoA/RhoC up-regulation, leading to Rho-kinase-associated cytoskeleton activation and breast tumor cell invasion. The Journal of biological chemistry 185 20843787
2002 Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability. The American journal of pathology 171 11839578
2013 MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PloS one 166 24376640
2011 A novel spatiotemporal RhoC activation pathway locally regulates cofilin activity at invadopodia. Current biology : CB 148 21474314
2013 RhoA, RhoB and RhoC have different roles in cancer cell migration. Journal of microscopy 139 23488932
2003 Atorvastatin prevents RhoC isoprenylation, invasion, and metastasis in human melanoma cells. Molecular cancer therapeutics 125 14578459
2004 Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma. Cancer research 124 15574779
2000 RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia (New York, N.Y.) 124 11191108
2012 miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer. International journal of oncology 121 22293682
2010 Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC. Oncogene 120 20101212
2002 XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. The Journal of biological chemistry 119 12221096
2008 RhoC promotes metastasis via activation of the Pyk2 pathway in prostate cancer. Cancer research 99 18794150
2005 RhoC-GTPase is a novel tissue biomarker associated with biologically aggressive carcinomas of the breast. Breast cancer research and treatment 91 16187229
2011 Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4. Molecular cancer therapeutics 89 22057916
2019 LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway. Journal of experimental & clinical cancer research : CR 85 31443665
2004 A definitive role of RhoC in metastasis of orthotopic lung cancer in mice. Clinical cancer research : an official journal of the American Association for Cancer Research 85 14871999
2002 Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer. Clinical & experimental metastasis 85 12090470
2005 Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and caveolin-1. Molecular cancer 80 15969750
2015 miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-α. Oncogene 78 25659578
2005 RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long-lasting specific changes following spinal cord injury. The Journal of comparative neurology 75 15736231
2004 WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer. Breast cancer research : BCR 72 14696649
2002 Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. Molecular cancer therapeutics 71 12479217
2023 Enhanced BCAT1 activity and BCAA metabolism promotes RhoC activity in cancer progression. Nature metabolism 70 37337119
2010 p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival. Cell research 68 21079653
2014 miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs. Journal of translational medicine 66 25236186
2006 Targeted disruption of protein kinase C epsilon reduces cell invasion and motility through inactivation of RhoA and RhoC GTPases in head and neck squamous cell carcinoma. Cancer research 65 17018591
2012 RhoC impacts the metastatic potential and abundance of breast cancer stem cells. PloS one 61 22911725
2006 RhoA and RhoC proteins promote both cell proliferation and cell invasion of human oesophageal squamous cell carcinoma cell lines in vitro and in vivo. European journal of cancer (Oxford, England : 1990) 61 16750623
2010 Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers. Cancer 60 20503409
2004 RhoC induces differential expression of genes involved in invasion and metastasis in MCF10A breast cells. Breast cancer research and treatment 60 14999149
2017 HIF-3α Promotes Metastatic Phenotypes in Pancreatic Cancer by Transcriptional Regulation of the RhoC-ROCK1 Signaling Pathway. Molecular cancer research : MCR 59 28928287
2015 RhoC is a major target of microRNA-93-5P in epithelial ovarian carcinoma tumorigenesis and progression. Molecular cancer 57 25649143
2012 ARHGAP21 is a RhoGAP for RhoA and RhoC with a role in proliferation and migration of prostate adenocarcinoma cells. Biochimica et biophysica acta 57 23200924
2006 RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility. Oncogene 57 16314838
2006 RhoC promotes human melanoma invasion in a PI3K/Akt-dependent pathway. The Journal of investigative dermatology 57 16470169
2003 Higher expression of RhoC is related to invasiveness in non-small cell lung carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 57 14614010
2013 Spatial regulation of RhoC activity defines protrusion formation in migrating cells. Journal of cell science 56 23704350
2022 A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology. Biochemical pharmacology 55 36306821
2011 SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC. The Journal of biological chemistry 55 21242305
2003 Expression and significance of RhoC gene in hepatocellular carcinoma. World journal of gastroenterology 55 12970882
2008 Inhibition of invasion and metastasis of hepatocellular carcinoma cells via targeting RhoC in vitro and in vivo. Clinical cancer research : an official journal of the American Association for Cancer Research 54 18980974
2006 RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck. Clinical cancer research : an official journal of the American Association for Cancer Research 54 16899593
2009 Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression. British journal of cancer 53 19953094
2012 Regulation of inflammatory breast cancer cell invasion through Akt1/PKBα phosphorylation of RhoC GTPase. Molecular cancer research : MCR 52 22896661
2011 p38γ promotes breast cancer cell motility and metastasis through regulation of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior. Cancer research 52 21862636
2016 Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling. Scientific reports 48 27991524
2014 Mouse macrophages completely lacking Rho subfamily GTPases (RhoA, RhoB, and RhoC) have severe lamellipodial retraction defects, but robust chemotactic navigation and altered motility. The Journal of biological chemistry 47 25213860
2013 Atorvastatin inhibits RhoC function and limits head and neck cancer metastasis. Oral oncology 47 23648017
2004 Expression of RHOC is associated with metastasis of gastric carcinomas. Pathobiology : journal of immunopathology, molecular and cellular biology 47 14555841
2007 RhoC is essential for the metastasis of gastric cancer. Journal of molecular medicine (Berlin, Germany) 46 17549441
2007 RhoA and RhoC -siRNA inhibit the proliferation and invasiveness activity of human gastric carcinoma by Rho/PI3K/Akt pathway. World journal of gastroenterology 46 17659701
2019 RhoC: a fascinating journey from a cytoskeletal organizer to a Cancer stem cell therapeutic target. Journal of experimental & clinical cancer research : CR 44 31340863
2014 Down regulation of RhoC by microRNA-138 results in de-activation of FAK, Src and Erk1/2 signaling pathway in head and neck squamous cell carcinoma. Oral oncology 44 24565984
2017 RhoA, RhoB and RhoC differentially regulate endothelial barrier function. Small GTPases 43 28949796
2014 RhoC regulates cancer stem cells in head and neck squamous cell carcinoma by overexpressing IL-6 and phosphorylation of STAT3. PloS one 43 24533098
2013 A RhoC biosensor reveals differences in the activation kinetics of RhoA and RhoC in migrating cells. PloS one 43 24224016
2011 The interaction of PKN3 with RhoC promotes malignant growth. Molecular oncology 42 22217540
2019 Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway. Cell communication and signaling : CCS 40 30683109
2018 Long non-coding RNA MT1DP shunts the cellular defense to cytotoxicity through crosstalk with MT1H and RhoC in cadmium stress. Cell discovery 39 29507753
2012 Role of the angiogenic components, VEGFA, FGF2, OPN and RHOC, in urothelial cell carcinoma of the urinary bladder. Oncology reports 39 22895562
2015 RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells. Journal of cell science 38 26136364
2016 MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC). Oncotarget 36 26673619
2016 The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 26741994
2016 Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma. Molecular cancer therapeutics 35 27837031
2015 Caveolin-1 mediates inflammatory breast cancer cell invasion via the Akt1 pathway and RhoC GTPase. Journal of cellular biochemistry 32 25559359
2014 The role of RhoC in epithelial-to-mesenchymal transition of ovarian carcinoma cells. BMC cancer 32 24986540
2013 Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB. Biochemistry 32 24128008
2009 RhoC expression and head and neck cancer metastasis. Molecular cancer research : MCR 32 19861405
2019 RhoC regulates radioresistance via crosstalk of ROCK2 with the DNA repair machinery in cervical cancer. Journal of experimental & clinical cancer research : CR 31 31488179
2012 RhoC regulates the proliferation of gastric cancer cells through interaction with IQGAP1. PloS one 31 23145020
2015 Inhibition of Ovarian Epithelial Carcinoma Tumorigenesis and Progression by microRNA 106b Mediated through the RhoC Pathway. PloS one 30 25933027
2009 The role of RhoC in growth and metastatic capacity of melanoma. Journal of cutaneous pathology 30 19222696
2008 Possible role of the RhoC/ROCK pathway in progression of clear cell renal cell carcinoma. Biomedical research (Tokyo, Japan) 30 18614849
2021 Role of RhoC in cancer cell migration. Cancer cell international 29 34627249
2020 RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells. Cell death & disease 28 33082325
2012 Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines. Cancer letters 28 23036489
2021 MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway. Analytical cellular pathology (Amsterdam) 27 33828938
2020 Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 32314833
2018 Transcriptional and post-transcriptional regulation of the genes encoding the small GTPases RhoA, RhoB, and RhoC: implications for the pathogenesis of human diseases. Cellular and molecular life sciences : CMLS 27 29500478
2017 RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6. Developmental cell 27 28486133
2014 Spatial regulation of tumor cell protrusions by RhoC. Cell adhesion & migration 27 24642482
2010 Farnesyl transferase inhibitor treatment of breast cancer cells leads to altered RhoA and RhoC GTPase activity and induces a dormant phenotype. International journal of cancer 27 20824700
2018 Formin-like 3 regulates RhoC/FAK pathway and actin assembly to promote cell invasion in colorectal carcinoma. World journal of gastroenterology 26 30228782
2011 ETS-1/RhoC signaling regulates the transcription factor c-Jun in melanoma. International journal of cancer 26 21732343
2011 RhoGDIα-dependent balance between RhoA and RhoC is a key regulator of cancer cell tumorigenesis. Molecular biology of the cell 26 21757538
2019 RhoC/ROCK2 promotes vasculogenic mimicry formation primarily through ERK/MMPs in hepatocellular carcinoma. Biochimica et biophysica acta. Molecular basis of disease 25 30779947
2009 Expression of RhoA and RhoC in colorectal carcinoma and its relations with clinicopathological parameters. Clinical chemistry and laboratory medicine 25 19499974
2009 Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity. Biological chemistry 25 19642867
2016 Knockdown of RHOC by shRNA suppresses invasion and migration of cholangiocellular carcinoma cells via inhibition of MMP2, MMP3, MMP9 and epithelial-mesenchymal transition. Molecular medicine reports 24 27108649
2015 RhoC and ROCKs regulate cancer cell interactions with endothelial cells. Molecular oncology 24 25677806
2011 RhoC protein stimulates migration of gastric cancer cells through interaction with scaffold protein IQGAP1. Molecular medicine reports 23 21537845

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