Affinage

BCAM

Basal cell adhesion molecule · UniProt P50895

Length
628 aa
Mass
67.4 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCAM (Lutheran/B-CAM/CD239) is a transmembrane immunoglobulin-superfamily receptor for the laminin alpha5 chain whose adhesive activity links extracellular basement membrane to intracellular signaling and the membrane skeleton (PMID:18032551, PMID:21434869). Its laminin-binding activity is switched on by PKA-dependent phosphorylation of its cytoplasmic tail downstream of cAMP signaling: in erythrocytes, beta-2 adrenergic/cAMP stimulation and the Epac/Rap1 axis drive BCAM-dependent adhesion to laminin (PMID:12506027, PMID:15613546), and the cytoplasmic tail is a substrate for PKA, CKII, and GSK3b (PMID:18514010). This same cAMP/Rap1/Akt cascade is constitutively engaged by JAK2V617F through an EpoR-independent Rap1/Akt pathway, explaining elevated BCAM phosphorylation and adhesion in polycythemia vera and sickle cell disease (PMID:17412890, PMID:23160466); hydroxyurea/hydroxycarbamide reverses this by lowering cAMP, in part through PDE4A upregulation (PMID:20566895, PMID:24616094). Adhesion is negatively regulated at two levels: direct binding of the cytoplasmic RK573-574 motif to spectrin dampens laminin binding and couples laminin engagement to RhoA-driven actin stress-fiber formation (PMID:20092464, PMID:21434869), and a cis-interaction with glycophorin-C sialic acid masks the receptor on healthy erythrocytes until Gardos-channel-driven shedding during senescence releases it into an adhesion-competent state (PMID:29344581, PMID:33351118). Beyond blood, BCAM is required in vivo for basement membrane organization in kidney and intestine (PMID:18032551), regulates biliary ductular morphogenesis in liver regeneration (PMID:30059007), and functions as a progenitor-state regulator in trophoblast and corneal epithelium (PMID:35020896, PMID:35947947). BCAM also serves as the high-affinity cell-surface receptor for E. coli Cytotoxic Necrotizing Factor 1 (CNF1) via its Ig-like domains (PMID:24453976, PMID:29267242), and is recurrently subverted in cancer, most strikingly through an oncogenic BCAM-AKT2 fusion that produces a constitutively active membrane-associated AKT2 kinase (PMID:25733895).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2002 High

    Established that BCAM/Lu adhesion to laminin is not constitutive but is switched on by an adrenergic cAMP/PKA signaling cascade, identifying a regulatable activation mechanism for the receptor.

    Evidence cAMP measurement, forskolin/epinephrine stimulation, PKA inhibition, and soluble BCAM/Lu competition adhesion assays in sickle RBCs

    PMID:12506027

    Open questions at the time
    • Did not map the phosphorylated residues on the cytoplasmic tail
    • Did not define the upstream nucleotide exchange machinery linking cAMP to BCAM
  2. 2004 High

    Connected the cAMP signal to a specific effector by showing Epac-mediated Rap1 activation is sufficient to drive BCAM-dependent, integrin-independent laminin adhesion.

    Evidence Rap1-GTP pull-down with Epac-specific cAMP analog and adhesion assays with BCAM/Lu competitor/blocking antibodies

    PMID:15613546

    Open questions at the time
    • Did not show how Rap1 connects to the BCAM phosphorylation event
    • Restricted to erythrocyte context
  3. 2004 Medium

    Provided direct gain-of-function evidence that B-CAM/laminin interaction can drive cell migration independent of integrins, extending the receptor's role beyond static adhesion.

    Evidence B-CAM overexpression in fibroblasts, haptotaxis on laminin with integrin blocking, and in situ B-CAM/Fc binding to tumor stroma

    PMID:15278364

    Open questions at the time
    • Single lab gain-of-function
    • Did not define downstream motility signaling
  4. 2006 High

    Showed BCAM/Lu can act as a counter-receptor for integrin alpha4beta1, broadening its adhesive partner repertoire beyond laminin.

    Evidence Adhesion assays under static/flow conditions with Lu-Fc chimera and soluble Lu-Fc/VCAM-1-Fc blocking

    PMID:17158232

    Open questions at the time
    • Did not establish in vivo relevance of the alpha4beta1 interaction
    • Binding stoichiometry/affinity not measured
  5. 2007 High

    Defined the physiological loss-of-function consequence of BCAM as a laminin alpha5 receptor, showing it is required for basement membrane organization in vivo.

    Evidence Lu/BCAM-null mice with histological analysis of kidney glomeruli and intestinal smooth muscle

    PMID:18032551

    Open questions at the time
    • Did not resolve the signaling mechanism underlying the structural defect
    • Phenotype restricted to two organ systems examined
  6. 2007 High

    Linked BCAM activation to myeloproliferative disease by showing JAK2V617F elevates BCAM expression and phosphorylation, driving pathological endothelial adhesion.

    Evidence JAK2V617F transfection into K562, phosphorylation/IP assays, and antibody-inhibited adhesion of PV RBCs

    PMID:17412890

    Open questions at the time
    • Intermediate signaling between JAK2 and BCAM not yet defined
    • Did not address EpoR involvement
  7. 2008 Medium

    Identified the kinases acting on the BCAM cytoplasmic tail, mechanistically grounding the cAMP/PKA activation model.

    Evidence In vitro kinase assays (CKII, GSK3b, PKA) and PKA-pathway-stimulated adhesion to laminin 10/11 in K562 transfectants

    PMID:18514010

    Open questions at the time
    • Proceedings/review format from single lab
    • Functional contribution of CKII/GSK3b sites versus PKA not dissected
  8. 2010 High

    Mapped a negative regulator by identifying the RK573-574 motif as the spectrin-skeleton attachment site whose disruption enhances laminin adhesion.

    Evidence Triton fractionation, RK->AA mutant K562 transfection, adhesion assays, validated in spectrin-deficient hereditary spherocytosis RBCs

    PMID:20092464

    Open questions at the time
    • Did not define the downstream signaling triggered by skeleton release
    • Spectrin isoform specificity not addressed
  9. 2010 High

    Provided a mechanistic rationale for a therapeutic by showing hydroxyurea reduces adhesion via lowered cAMP and BCAM dephosphorylation without altering expression.

    Evidence cAMP measurement, phosphorylation and adhesion assays in patient RBCs and a recombinant BCAM cell model

    PMID:20566895

    Open questions at the time
    • Mechanism by which hydroxyurea lowers cAMP not yet defined at this stage
  10. 2011 High

    Resolved the spectrin interaction into a bidirectional signaling relay, showing BCAM-alphaII-spectrin binding controls surface half-life and transmits laminin signals to RhoA-driven actin reorganization.

    Evidence Co-IP, RK573-574AA mutagenesis, MDCK adhesion/spreading assays, RhoA pull-down, and actin staining

    PMID:21434869

    Open questions at the time
    • RhoA activation mechanism downstream of BCAM not fully mapped
    • Single-lab study
  11. 2012 High

    Defined the JAK2V617F-to-BCAM pathway as an EpoR-independent Rap1/Akt cascade, unifying the cAMP and oncogenic activation routes onto Rap1.

    Evidence Rap1-GTP/Akt assays, dominant-negative Rap1S17N, GGTI-298 inhibition, EpoR siRNA, and adhesion assays in HEL/BaF3 cells and PV RBCs

    PMID:23160466

    Open questions at the time
    • Direct kinase linking Akt to BCAM phosphorylation not identified
    • Relationship to the PKA route not reconciled
  12. 2013 Medium

    Revealed a context-dependent tumor-suppressive role for BCAM in hepatoma and showed its transcription is repressed by the 14-3-3beta-FBI1/Akirin2 complex.

    Evidence BCAM forced expression in K2 hepatoma with growth/migration/invasion/tumorigenicity assays, luciferase reporter, and ChIP

    PMID:24223164

    Open questions at the time
    • Single lab and single cell model
    • Mechanism of growth suppression downstream of BCAM not defined
  13. 2014 High

    Identified BCAM/Lu as the obligate cell-surface receptor for E. coli CNF1 toxin, assigning a host-pathogen interaction function.

    Evidence Tagged-toxin co-precipitation, competition, and CNF1 binding loss in Lu/BCAM-deficient cells expressing p37LRP

    PMID:24453976

    Open questions at the time
    • Did not yet define the binding domain or affinity
    • Internalization route of toxin via BCAM not established
  14. 2014 High

    Extended the hydroxyurea mechanism to endothelium, showing PDE4A upregulation lowers cAMP and BCAM phosphorylation on the vessel side of the adhesion.

    Evidence Adhesion, phosphorylation, cAMP, and PDE4A expression assays in bone marrow and pulmonary microvascular endothelial cells

    PMID:24616094

    Open questions at the time
    • How hydroxycarbamide induces PDE4A not defined
    • Endothelial BCAM ligand engagement not fully mapped
  15. 2014 Medium

    Quantified single-receptor activation at the molecular level, showing AKAP-dependent cAMP/PKA signaling increases the number and unbinding force of active BCAM-laminin bonds.

    Evidence Single-molecule atomic force microscopy with cAMP-pathway and AKAP manipulation in patient RBCs

    PMID:24655501

    Open questions at the time
    • Single-lab biophysical study
    • Identity of the relevant AKAP not specified
  16. 2015 High

    Demonstrated oncogenic gain-of-function via a recurrent BCAM-AKT2 fusion producing a membrane-anchored, constitutively active AKT2 kinase.

    Evidence RT-PCR/sequencing, kinase and phosphorylation assays, and CRISPR/Cas9-recapitulated fusion driving focus formation in OVCAR8/HEK-293T

    PMID:25733895

    Open questions at the time
    • Contribution of the BCAM extracellular/transmembrane portion to oncogenicity not dissected
    • In vivo tumorigenesis of the fusion not tested
  17. 2016 High

    Showed BCAM-LAMA5 recognition mediates endothelial adhesion specific to KRAS-mutant colorectal cancer cells during metastatic spreading, a targetable interaction.

    Evidence Phage display, genetic KD plus biochemical inhibition of BCAM/LAMA5, patient IHC, and BCAM-mimic peptide inhibition of mouse metastasis

    PMID:27143691

    Open questions at the time
    • Signaling consequences of the adhesion in cancer cells not defined
    • KRAS-to-BCAM regulatory link not mechanistically resolved
  18. 2017 High

    Localized and quantified the CNF1 interaction, mapping high-affinity binding to BCAM Ig-like domain 2 and defining the complex architecture.

    Evidence Surface plasmon resonance (KD = 2.8 nM) and small-angle X-ray scattering of the Lu/BCAM-CNF1 complex

    PMID:29267242

    Open questions at the time
    • No high-resolution atomic structure of the complex
    • Functional consequence of the 6:1 stoichiometry unknown
  19. 2018 High

    Defined a cis-masking mechanism in which glycophorin-C sialic acid suppresses BCAM laminin binding via the third Ig-like domain until sialic acid loss during erythrocyte aging unmasks it.

    Evidence Laminin-alpha5 binding assays, sialic acid depletion, Gerbich (GPC-null) erythrocytes, domain mapping, and neuraminidase treatment

    PMID:29344581

    Open questions at the time
    • Did not define the cellular trigger driving GPC release in vivo at this stage
    • Structural basis of the cis-complex unresolved
  20. 2018 High

    Established a developmental/regenerative role, showing BCAM cell-autonomously promotes biliary cell motility and duct formation and is required for the ductular reaction after liver injury.

    Evidence Lu+ vs Lu- biliary cell motility/duct assays, Lu overexpression rescue, and Lu-knockout mouse liver injury models

    PMID:30059007

    Open questions at the time
    • Downstream signaling controlling motility/morphogenesis not defined
    • Ligand engaged during ductular reaction not specified
  21. 2018 Medium

    Showed CD239/BCAM is internalized in breast cancer cells, enabling receptor-mediated antibody-drug conjugate killing of high-expressing tumor cells.

    Evidence Expression/internalization assays and anti-CD239 scFv-Fc-diphtheria toxin cytotoxicity in SKBR3 cells

    PMID:29700410

    Open questions at the time
    • Internalization route and trafficking not defined
    • Single-lab proof of concept
  22. 2020 High

    Identified the upstream trigger for erythrocyte BCAM activation, showing Gardos-channel-driven shedding of GPC vesicles removes cis-suppression during senescence.

    Evidence Gardos channel activation/inhibition, GPC vesicle shedding measurement, and BCAM activity assays in sickle, stored, and dehydrated RBCs

    PMID:33351118

    Open questions at the time
    • Link between Ca2+/K+ flux and vesicle shedding not fully mechanistic
    • Relevance to non-erythroid BCAM regulation unknown
  23. 2022 Medium

    Established BCAM as a functional regulator of trophoblast progenitor maintenance and differentiation in the placenta.

    Evidence scRNA-seq of first-trimester placenta with BCAM gain-of-function and siRNA silencing in trophoblast organoids

    PMID:35020896

    Open questions at the time
    • Signaling pathway controlling progenitor state not defined here
    • Single-lab organoid study
  24. 2022 Medium

    Defined BCAM as a p63-regulated marker and functional requirement of proliferative corneal epithelial progenitors.

    Evidence FACS isolation of BCAM+ limbal cells, holoclone/sheet generation, BCAM knockdown migration/differentiation assays, and p63 manipulation

    PMID:35947947

    Open questions at the time
    • Downstream effectors of BCAM in progenitors not defined
    • Single-lab study
  25. 2022 Medium

    Connected BCAM to a defined intracellular signaling pathway in trophoblast and to preeclampsia pathophysiology via PIK3R6/p-STAT3 signaling.

    Evidence BCAM siRNA in HTR-8/SVneo and JAR cells with proliferation/migration/invasion and STAT3 assays, plus adenoviral BCAM shRNA in pregnant rats

    PMID:36252138

    Open questions at the time
    • Mechanistic link between BCAM and PIK3R6 not resolved
    • Single-lab study
  26. 2024 Low

    Implicated BCAM as a downstream effector of a histone lactylation epigenetic program driving oral squamous cell carcinoma aggressiveness.

    Evidence Bioinformatics with experimental validation of BCAM in OSCC invasion, angiogenesis, and cisplatin resistance

    PMID:39503345

    Open questions at the time
    • Methods poorly specified and primarily bioinformatics-driven
    • Direct link from histone lactylation to BCAM transcription not mechanistically established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cytoplasmic phosphorylation/spectrin switch is mechanistically coupled to the diverse non-erythroid roles of BCAM (developmental progenitor maintenance, ductular morphogenesis, cancer signaling) remains unresolved.
  • No structure of full-length BCAM with bound laminin/spectrin
  • The kinase directly phosphorylating BCAM downstream of Akt not identified
  • Unifying signaling logic across tissues not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2
Partners
AKT2CNF1GYPCITGA4LAMA5SPTAN1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Epinephrine and cAMP activate sickle RBC adhesion to laminin via BCAM/Lu in a protein kinase A (PKA)-dependent manner. Elevated cAMP in sickle RBCs (>4-fold over normal) is further increased by forskolin or epinephrine, and adhesion is blocked by recombinant soluble BCAM/Lu, implicating PKA-dependent phosphorylation of BCAM/Lu in laminin binding. The beta-2 adrenergic receptor mediates epinephrine-stimulated adhesion. cAMP measurement, pharmacological stimulation (forskolin, epinephrine, PKA inhibitors), adhesion assay with soluble BCAM/Lu as competitor, beta-adrenergic receptor blocking Blood High 12506027
2004 Epac-mediated Rap1 activation in sickle RBCs promotes BCAM/Lu-dependent adhesion to laminin. The Epac-specific cAMP analog 8CPT-2-Me activates Rap1 and induces SS RBC adhesion to laminin that is completely inhibited by soluble BCAM/Lu or a BCAM/Lu adhesion-blocking antibody, and is independent of integrin alpha4beta1. Rap1-GTP pull-down, cAMP analog stimulation, adhesion assay with BCAM/Lu competitor and blocking antibodies, RGD peptide/integrin antibody controls Blood High 15613546
2006 Endothelial Lu/BCAM glycoproteins interact with integrin alpha4beta1 on immature sickle reticulocytes. Using chimeric Lu-Fc protein and cell adhesion assays under static and flow conditions, epinephrine-stimulated sickle RBCs adhere to Lu-Fc via alpha4beta1, and this adhesion is inhibited by soluble Lu-Fc and VCAM-1-Fc. Cell adhesion assays (static and flow conditions), transfected cell lines expressing alpha4beta1, chimeric Lu-Fc protein, blocking with soluble Lu-Fc and VCAM-1-Fc Blood High 17158232
2007 Lu/BCAM phosphorylation is constitutively elevated in polycythemia vera (PV) RBCs. JAK2(V617F) transfection into K562 cells increases Lu/BCAM expression and phosphorylation, and adhesion of PV RBCs to endothelial cells is inhibited by anti-Lu/BCAM or anti-laminin alpha5 antibodies. Flow cytometry, immunoprecipitation/phosphorylation assays, K562 transfection, radiometric adhesion assay, antibody inhibition, JAK2 V617F plasmid transfection Blood High 17412890
2008 Lu/BCAM long isoform (Lu) cytoplasmic tail is phosphorylated by CKII, GSK3b, and PKA. Phosphorylation of Lu in transfected K562 cells by PKA pathway effectors stimulates cell adhesion to laminin 10/11. In vitro kinase assays, K562 cell transfection, PKA pathway stimulation, cell adhesion assays Transfusion clinique et biologique Medium 18514010
2007 Lu/BCAM-null mice develop glomerular basement membrane abnormalities (reduced capillary lumens, irregular GBM thickening) and intestinal smooth muscle coat thickening/disorganization, demonstrating that Lu/BCAM, as a laminin alpha5 receptor, is required in vivo for normal basement membrane organization in kidney and intestine. Genetic knockout (Lu/BCAM-null mice), histological analysis of kidney and intestine, renal function tests American Journal of Physiology - Renal Physiology High 18032551
2010 Hydroxyurea reduces sickle RBC adhesion to laminin by decreasing intracellular cAMP levels, thereby diminishing PKA-dependent Lu/BCAM phosphorylation, without reducing Lu/BCAM expression. Demonstrated in patient RBCs and a cellular model expressing recombinant Lu/BCAM. cAMP measurement, phosphorylation assay, adhesion assay, hydroxyurea treatment of patients and cell model Blood High 20566895
2010 Lu/BCAM interacts with the spectrin-based membrane skeleton via its RK573-574 motif. In hereditary spherocytosis (HS) RBCs with spectrin deficiency, a greater fraction of Lu/BCAM is unlinked from the skeleton, and disruption of the spectrin interaction site in K562 transfectants weakens skeleton binding and enhances adhesion to laminin, demonstrating that spectrin interaction negatively regulates Lu/BCAM-mediated laminin adhesion. Triton extraction fractionation, K562 transfection with RK→AA mutant Lu/BCAM, cell adhesion assay, soluble Lu/BCAM blocking British Journal of Haematology High 20092464
2011 Lu/BCAM binds non-erythroid αII-spectrin via its RK573-574 motif. Alanine substitution of this motif abolishes spectrin binding, enhances Lu/BCAM surface half-life, increases Lu/BCAM-mediated cell adhesion/spreading on laminin 511/521, and mediates actin reorganization into stress fibers through a laminin-to-actin signaling pathway involving RhoA activation. Spectrin acts as a signal relay between laminin 511/521 and actin. Co-immunoprecipitation, site-directed mutagenesis (RK573-574AA), MDCK cell expression, adhesion and spreading assays, RhoA activation assay (pull-down), actin staining The Biochemical Journal High 21434869
2012 JAK2V617F activates Lu/BCAM phosphorylation and laminin adhesion through an EpoR-independent Rap1/Akt pathway. In HEL and BaF3 cells expressing JAK2V617F, Rap1-GTP and Akt activity are elevated, leading to Lu/BCAM phosphorylation and laminin adhesion; these are inhibited by dominant-negative Rap1S17N or the Rap1 inhibitor GGTI-298. EpoR knockdown does not alter Akt activity or laminin adhesion. Rap1-GTP pull-down, Akt activity assay, Lu/BCAM phosphorylation assay, dominant-negative Rap1 overexpression, pharmacological inhibition (GGTI-298), EpoR siRNA knockdown, cell adhesion assay Blood High 23160466
2014 Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelial cells by inhibiting endothelial Lu/BCAM phosphorylation through upregulation of phosphodiesterase 4A (PDE4A) expression, which reduces cAMP-dependent signaling. This was demonstrated in transformed bone marrow endothelial cells and primary pulmonary microvascular endothelial cells. Cell adhesion assay, Lu/BCAM phosphorylation assay, cAMP measurement, PDE4A expression analysis, pharmacological hydroxycarbamide treatment of endothelial cells The Journal of Biological Chemistry High 24616094
2014 Lu/BCAM is the cellular receptor for E. coli Cytotoxic Necrotizing Factor 1 (CNF1). CNF1 binds to Lu/BCAM via amino acids 720–1014 of CNF1; cells deficient in Lu/BCAM but expressing p37LRP cannot bind CNF1 at the cell surface, establishing that Lu/BCAM is essential for CNF1 cell surface binding and toxin action. Co-precipitation of cell surface molecules with tagged toxin, direct protein-protein interaction analysis, competition studies, Lu/BCAM-deficient cell lines PLoS Pathogens High 24453976
2015 A recurrent BCAM-AKT2 gene fusion in high-grade serous ovarian carcinoma produces a membrane-associated, constitutively phosphorylated and activated AKT2 kinase fusion protein. CRISPR/Cas9-generated BCAM-AKT2 fusion leads to focus formation in OVCAR8 and HEK-293T cells, demonstrating oncogenic activity. RT-PCR/sequencing identification of fusion, Western blot for phosphorylation, functional kinase assay, CRISPR/Cas9 chromosomal translocation generation, focus formation assay Proceedings of the National Academy of Sciences of the USA High 25733895
2016 BCAM and LAMA5 (laminin alpha5) mediate recognition between KRAS-mutant colorectal cancer cells and endothelial cells in metastatic spreading. Genetic suppression or biochemical inhibition of BCAM or LAMA5 impairs adhesion of KRAS-mutant cells specifically to endothelial cells (not pericytes or hepatocytes), and BCAM-mimic peptides inhibit metastasis in mouse models. Phage display screening, adhesion assays (genetic KD and biochemical inhibition), immunohistochemistry on patient specimens, mouse metastasis models with BCAM-mimic peptides Clinical Cancer Research High 27143691
2017 High-affinity binding of CNF1 to Lu/BCAM occurs via the Ig-like domain 2 of Lu/BCAM (KD = 2.8 nM by surface plasmon resonance). Small-angle X-ray scattering of the Lu/BCAM-CNF1 complex suggests a 6:1 ratio of Lu/BCAM to CNF1. Surface plasmon resonance, direct protein-protein interaction analysis, small-angle X-ray scattering (SAXS) Toxins High 29267242
2018 Lu/BCAM-mediated binding to laminin-alpha5 on healthy erythrocytes is suppressed by interaction in cis with glycophorin-C (GPC)-derived sialic acid residues. Upon erythrocyte aging and sialic acid loss, Lu/BCAM is released from GPC and can interact with sialic acid on laminin-alpha5. The sialic acid-binding site was identified within the third Ig-like domain of Lu/BCAM. Neuraminidase-expressing bacteria (e.g., S. pneumoniae) similarly induce Lu/BCAM activation. Laminin-alpha5 binding assays, sialic acid depletion experiments, GPC-knockout (Gerbich phenotype) erythrocytes, domain mapping, neuraminidase treatment Blood Advances High 29344581
2018 Lu/BCAM overexpression in biliary cells promotes cell motility and duct formation capacity (Lu+ biliary cells have opposite phenotypes to Lu- cells). Lu-deficient mice show severe defects in ductular reaction following liver injury. Overexpression of Lu in Lu- biliary cells converts their phenotype to that of Lu+ cells, demonstrating a direct role in biliary morphogenesis. Isolation and in vitro culture of Lu+ vs Lu- biliary cells, motility and duct formation assays, Lu overexpression in Lu- cells, Lu-knockout mouse liver injury model eLife High 30059007
2013 BCAM acts as a suppressive oncoprotein: BCAM-expressing hepatoma K2 cells lose malignant characteristics (anchorage-independent growth, migration, invasion, tumorigenicity). The 14-3-3β-FBI1/Akirin2 complex binds the BCAM promoter and represses BCAM transcription, as shown by luciferase reporter assays and chromatin immunoprecipitation. BCAM forced expression in K2 hepatoma cells, anchorage-independent growth/migration/invasion/tumorigenicity assays, luciferase reporter assay, chromatin immunoprecipitation PLoS ONE Medium 24223164
2004 B-CAM overexpression in fibroblasts enhances haptotactic migration on laminin matrix when integrin-mediated adhesion is blocked, providing direct experimental evidence that B-CAM/laminin interactions mediate cell migration. B-CAM/Fc chimeric protein binds to peritumoral stroma in skin cancer specimens in situ. B-CAM overexpression in murine and human fibroblasts, haptotaxis migration assay on laminin, integrin blocking by EDTA chelation, in situ B-CAM/Fc binding to tissue sections Archives of Dermatological Research Medium 15278364
2020 The Gardos effect (Ca2+-dependent K+ efflux via the Gardos channel) drives erythrocyte senescence and activates Lu/BCAM. GPC-derived sialic acid residues suppress Lu/BCAM activity via cis-complex on the erythrocyte membrane; Gardos channel-mediated shedding of GPC vesicles removes this suppression, releasing Lu/BCAM to become adhesion-competent. Gardos channel activation/inhibition, glycophorin-C vesicle shedding measurement, Lu/BCAM activity assays, erythrocyte dehydration models, transfusion/storage models, sickle cell samples Blood Advances High 33351118
2014 A-kinase anchoring proteins (AKAPs) are crucial for BCAM/Lu receptor activation on RBC surfaces. Single-molecule atomic force microscopy shows that expression of active BCAM/Lu receptors is higher on sickle RBCs than normal, depends critically on the cAMP/PKA signaling pathway, and is reduced by hydroxyurea treatment. Epinephrine stimulation increases BCAM/Lu-laminin unbinding force on sickle cell trait RBCs. Atomic force microscopy (single-molecule force spectroscopy), cAMP pathway pharmacological manipulation, hydroxyurea-treated patient samples, AKAP inhibition Biophysical Journal Medium 24655501
2022 BCAM marks a primitive cytotrophoblast progenitor state in the placenta. BCAM enrichment or gene silencing results in enhanced or diminished trophoblast organoid growth, respectively, establishing BCAM as a functional regulator of CTB progenitor maintenance and differentiation. Single-cell RNA sequencing of first-trimester placentas, trophoblast organoid system, BCAM gain-of-function and siRNA gene silencing, organoid growth quantification Development Medium 35020896
2022 Limbal BCAM-positive cells represent a highly proliferative corneal epithelial progenitor subpopulation capable of holoclone formation and corneal sheet generation. BCAM is functionally required for cellular migration and differentiation of corneal epithelial progenitors, and its expression is regulated by the transcription factor p63. FACS isolation of BCAM+ limbal cells, holoclone/paraclone formation assays, corneal sheet generation, loss-of-function (BCAM knockdown) migration and differentiation assays, p63 transcription factor manipulation Cell Reports Medium 35947947
2022 BCAM deficiency (induced by miR-199a-5p) in trophoblast cells suppresses trophoblast proliferation, migration, and invasion by inhibiting PIK3R6/p-STAT3 (Y705) signaling. In vivo, adenoviral BCAM shRNA delivery in pregnant rats induces a preeclampsia-like phenotype with elevated blood pressure, proteinuria, and fetal growth restriction, associated with downregulated BCAM/PIK3R6/p-STAT3 signaling. BCAM knockdown (siRNA) in HTR-8/SVneo and JAR cells, proliferation/migration/invasion assays, STAT3 phosphorylation assay, PIK3R6 expression analysis, dual-luciferase reporter for miR-199a-5p targeting, in vivo adenoviral shRNA delivery in pregnant rats Hypertension Medium 36252138
2018 CD239/BCAM is strongly expressed in a subset of breast cancer cells and is internalized into the cells. An anti-CD239 scFv-Fc antibody conjugated to diphtheria toxin fragment (fDT) selectively kills CD239-highly positive breast cancer cells (SKBR3), but not weakly positive cells, demonstrating receptor-mediated internalization enabling antibody-drug conjugate activity. Flow cytometry and immunostaining for CD239 expression, internalization assays, anti-CD239 scFv-Fc production, fDT-conjugate cytotoxicity assay Scientific Reports Medium 29700410
2024 Histone lysine lactylation (Kla)-induced upregulation of BCAM promotes OSCC (oral squamous cell carcinoma) invasion, angiogenesis, and cisplatin resistance, identifying BCAM as a downstream effector of the Kla epigenetic program in OSCC. Bioinformatics (TCGA/GEO), Cox prognostic model, experimental validation of BCAM role in OSCC invasion, angiogenesis, and drug resistance assays Oral Diseases Low 39503345

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. The New England journal of medicine 2491 28076709
2022 [177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Pharmaceuticals (Basel, Switzerland) 216 36297404
2016 Nephrotoxicity after PRRT with (177)Lu-DOTA-octreotate. European journal of nuclear medicine and molecular imaging 134 27160225
2002 Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion. Blood 130 12506027
2021 First-In-Human Results on the Biodistribution, Pharmacokinetics, and Dosimetry of [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2. Pharmaceuticals (Basel, Switzerland) 108 34959613
2007 Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin alpha5 chain and Lu/BCAM. Blood 104 17412890
2019 177Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors. Expert review of gastroenterology & hepatology 103 31652074
2024 Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in patients with metastatic hormone-sensitive prostate cancer (UpFrontPSMA): a multicentre, open-label, randomised, phase 2 study. The Lancet. Oncology 97 39293461
2018 Neuroendocrine Tumor Therapy: 177Lu-DOTATATE. AJR. American journal of roentgenology 92 29949416
2012 JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway. Blood 78 23160466
2020 Radiation doses from 161Tb and 177Lu in single tumour cells and micrometastases. EJNMMI physics 75 32430671
2022 Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Molecular diagnosis & therapy 70 35553387
2010 Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation. Blood 60 20566895
2022 Cell trajectory modeling identifies a primitive trophoblast state defined by BCAM enrichment. Development (Cambridge, England) 59 35020896
2016 BCAM and LAMA5 Mediate the Recognition between Tumor Cells and the Endothelium in the Metastatic Spreading of KRAS-Mutant Colorectal Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 59 27143691
2005 Review: Lutheran/B-CAM: a laminin receptor on red blood cells and in various tissues. Connective tissue research 50 16546822
2024 Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. European journal of nuclear medicine and molecular imaging 49 39060377
2021 Overcoming nephrotoxicity in peptide receptor radionuclide therapy using [177Lu]Lu-DOTA-TATE for the treatment of neuroendocrine tumours. Nuclear medicine and biology 48 34242948
2004 Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU. Blood 48 15613546
2006 Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell alpha4beta1 integrin: role in adhesion of sickle red blood cells to endothelial cells. Blood 45 17158232
2022 AlphaBet: Combination of Radium-223 and [17 7Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol). Frontiers in medicine 44 36465905
2019 Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 43 31757844
2015 Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma. Proceedings of the National Academy of Sciences of the United States of America 43 25733895
2020 Radioligand therapy using [177Lu]Lu-PSMA-617 in mCRPC: a pre-VISION single-center analysis. European journal of nuclear medicine and molecular imaging 40 32062682
2021 CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather. European journal of nuclear medicine and molecular imaging 39 33550492
2023 Development of [177Lu]Lu-LNC1003 for radioligand therapy of prostate cancer with a moderate level of PSMA expression. European journal of nuclear medicine and molecular imaging 38 37097443
2021 CD38-Targeted Theranostics of Lymphoma with 89Zr/177Lu-Labeled Daratumumab. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 38 34026426
2019 Concomitant 177Lu-DOTATATE and capecitabine therapy in malignant paragangliomas. EJNMMI research 38 30725219
2019 Therapy With 177Lu-DOTATATE: Clinical Implementation and Impact on Care of Patients With Neuroendocrine Tumors. AJR. American journal of roentgenology 38 31039017
2021 Efficacy and Safety of 177Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 37 34049983
2019 Evolution and Medical Significance of LU Domain-Containing Proteins. International journal of molecular sciences 37 31195646
2017 Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors. Nuclear medicine and molecular imaging 36 29942399
2014 Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation. The Journal of biological chemistry 35 24616094
2021 90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans. Pharmaceutics 33 34575538
2014 Lu/BCAM adhesion glycoprotein is a receptor for Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1). PLoS pathogens 33 24453976
2020 The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation. Blood advances 30 33351118
2007 Genetic inactivation of the laminin alpha5 chain receptor Lu/BCAM leads to kidney and intestinal abnormalities in the mouse. American journal of physiology. Renal physiology 29 18032551
2021 Biokinetics and Dosimetry of 177Lu-Pentixather. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 28 34413147
2024 Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 27 38724277
2021 Intraarterial Administration Boosts 177Lu-HA-DOTATATE Accumulation in Salvage Meningioma Patients. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 27 34301783
2024 Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 25 39266289
2008 Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 25 18514010
2024 Targeting CXCR4/CXCL12 axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 with CXCR4 antagonist in triple-negative breast cancer. European journal of nuclear medicine and molecular imaging 24 38587644
2023 [177Lu]Lu-PSMA-Radioligand Therapy Efficacy Outcomes in Taxane-Naïve Versus Taxane-Treated Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Metaanalysis. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24 37169534
2023 [177Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models. European journal of nuclear medicine and molecular imaging 24 38062170
2024 Multivariable models of outcomes with [177Lu]Lu-PSMA-617: analysis of the phase 3 VISION trial. EClinicalMedicine 23 39430616
2019 [68Ga]Ga/[177Lu]Lu-BL01, a Novel Theranostic Pair for Targeting C-X-C Chemokine Receptor 4. Molecular pharmaceutics 23 31545614
2018 Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte aging. Blood advances 23 29344581
2012 DARC (Duffy) and BCAM (Lutheran) reduced expression in thyroid cancer. Blood cells, molecules & diseases 23 23168236
1994 Non-polarized expression of Basal-cell adhesion molecule B-cam in epithelial ovarian cancers. International journal of oncology 23 21559707
2023 The predictive value of pretherapy [68Ga]Ga-DOTA-TATE PET and biomarkers in [177Lu]Lu-PRRT tumor dosimetry. European journal of nuclear medicine and molecular imaging 22 37171633
2022 Relationships between uptake of [68Ga]Ga-DOTA-TATE and absorbed dose in [177Lu]Lu-DOTA-TATE therapy. EJNMMI research 22 36534192
2020 Formulation and clinical translation of [177Lu]Lu-trastuzumab for radioimmunotheranostics of metastatic breast cancer. RSC medicinal chemistry 22 34046615
2013 The FBI1/Akirin2 target gene, BCAM, acts as a suppressive oncogene. PloS one 22 24223164
2012 Epinephrine modulates BCAM/Lu and ICAM-4 expression on the sickle cell trait red blood cell membrane. Biophysical journal 22 22404936
2010 Role of the interaction between Lu/BCAM and the spectrin-based membrane skeleton in the increased adhesion of hereditary spherocytosis red cells to laminin. British journal of haematology 21 20092464
2004 Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer. Archives of dermatological research 21 15278364
2000 Expression of the basal cell adhesion molecule (B-CAM) in normal and diseased human skin. Journal of cutaneous pathology 20 10728810
2024 Exploring the role of combined external beam radiotherapy and targeted radioligand therapy with [177Lu]Lu-PSMA-617 for prostate cancer - from bench to bedside. Theranostics 19 38646643
2011 Novel role for the Lu/BCAM-spectrin interaction in actin cytoskeleton reorganization. The Biochemical journal 19 21434869
2022 [68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma. Frontiers in oncology 18 36119502
2022 BCAM Deficiency May Contribute to Preeclampsia by Suppressing the PIK3R6/p-STAT3 Signaling. Hypertension (Dallas, Tex. : 1979) 18 36252138
2022 Response to targeted radionuclide therapy with [131I]MIBG AND [177Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review. Frontiers in endocrinology 18 36339441
2021 Modeling Early Radiation DNA Damage Occurring During 177Lu-DOTATATE Radionuclide Therapy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 18 34503959
2020 Extravasation of [177Lu]Lu-DOTATOC: case report and discussion. EJNMMI research 18 32577838
2025 Dosimetry of [177Lu]Lu-DOTATATE in Patients with Advanced Midgut Neuroendocrine Tumors: Results from a Substudy of the Phase III NETTER-1 Trial. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 17 39947918
2023 Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer. European journal of nuclear medicine and molecular imaging 17 38135849
2010 Role of Lu/BCAM glycoproteins in red cell diseases. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 17 20655789
2023 Radionuclide Therapy of HER2-Expressing Xenografts Using [177Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab. Cancers 16 37173878
2022 Limbal BCAM expression identifies a proliferative progenitor population capable of holoclone formation and corneal differentiation. Cell reports 16 35947947
2021 Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC. European journal of nuclear medicine and molecular imaging 16 33452632
2023 First preclinical evaluation of [225Ac]Ac-DOTA-JR11 and comparison with [177Lu]Lu-DOTA-JR11, alpha versus beta radionuclide therapy of NETs. EJNMMI radiopharmacy and chemistry 15 37389800
2022 Toxicity Assessment of [177Lu]Lu-iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes. Nanomaterials (Basel, Switzerland) 15 36500804
2020 Lutetium Lu-177 Dotatate Flare Reaction. Advances in radiation oncology 15 33490736
2022 Peptide Receptor Radionuclide Therapy with [177Lu]Lu-DOTA-TATE in Patients with Advanced GEP NENS: Present and Future Directions. Cancers 14 35158852
2022 [177Lu]Lu-DOTA-TATE and [131I]MIBG Phenotypic Imaging-Based Therapy in Metastatic/Inoperable Pheochromocytomas and Paragangliomas: Comparative Results in a Single Center. Frontiers in endocrinology 14 35197929
2020 Evaluation of [131I]I- and [177Lu]Lu-DTPA-A11 Minibody for Radioimmunotherapy in a Preclinical Model of PSCA-Expressing Prostate Cancer. Molecular imaging and biology 14 32661830
2014 AKAP-dependent modulation of BCAM/Lu adhesion on normal and sickle cell disease RBCs revealed by force nanoscopy. Biophysical journal 14 24655501
2021 The Safety and Efficacy of the Repeated PRRT with [90Y]Y/[177Lu]Lu-DOTATATE in Patients with NET. International journal of endocrinology 13 33552155
2018 Internalization of CD239 highly expressed in breast cancer cells: a potential antigen for antibody-drug conjugates. Scientific reports 13 29700410
2024 Imaging and Downstaging Bladder Cancer with the 177Lu-Labeled Bioorthogonal Nanoprobe. ACS nano 12 38904444
2023 Correlations between [68Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [177Lu]Lu-DOTA-TATE. Cancers 12 36831477
2023 Characterization of Non-Specific Uptake and Retention Mechanisms of [177Lu]Lu-PSMA-617 in the Salivary Glands. Pharmaceuticals (Basel, Switzerland) 12 37242475
2022 Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE. EJNMMI physics 12 35347483
2017 High Affinity Binding of Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) to Lu/BCAM Adhesion Glycoprotein. Toxins 12 29267242
2025 Long-Term Outcomes in Radioiodine-Resistant Follicular Cell-Derived Thyroid Cancers Treated with [177Lu]Lu-DOTAGA.FAPi Dimer Therapy. Thyroid : official journal of the American Thyroid Association 11 39869019
2024 Combining [177Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer. European journal of nuclear medicine and molecular imaging 11 39023784
2023 Inhibition of Poly(ADP-ribose) Polymerase Sensitizes [177Lu]Lu-DOTAGA.(SA.FAPi)2-Mediated Radiotherapy in Triple-Negative Breast Cancer. Molecular pharmaceutics 11 37067162
2021 p53-Mediated Radiosensitization of 177Lu-DOTATATE in Neuroblastoma Tumor Spheroids. Biomolecules 11 34827693
2025 Initial clinical experience with [177Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial. Frontiers in oncology 10 39839782
2025 Therapy-Related Myeloid Neoplasms After [177Lu]Lu-PSMA Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Case Series. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 10 39978813
2024 Dosimetry and pharmacokinetics of [177Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours. European journal of nuclear medicine and molecular imaging 10 38528164
2024 Initial Experience with [177Lu]Lu-PSMA-617 After Regulatory Approval for Metastatic Castration-Resistant Prostate Cancer: Efficacy, Safety, and Outcome Prediction. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 10 39299783
2024 Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance. Oral diseases 10 39503345
2023 Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Drugs of today (Barcelona, Spain : 1998) 10 36811416
2023 Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy. Journal of medicinal chemistry 10 37670407
2023 Estimation of relative biological effectiveness of 225Ac compared to 177Lu during [225Ac]Ac-PSMA and [177Lu]Lu-PSMA radiopharmaceutical therapy using TOPAS/TOPAS-nBio/MEDRAS. EJNMMI physics 10 37695374
2018 Differential expression of Lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration. eLife 10 30059007
2024 Outcomes for Patients with Metastatic Castration-Resistant Prostate Cancer and Liver Metastasis Receiving [177Lu]Lu-PSMA-617. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 9 39477495
2023 Radiobiological Assessment of Targeted Radionuclide Therapy with [177Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models. International journal of molecular sciences 9 38069337

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