Affinage

CMTM6

CKLF-like MARVEL transmembrane domain-containing protein 6 · UniProt Q9NX76

Length
183 aa
Mass
20.4 kDa
Annotated
2026-06-09
75 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CMTM6 is a transmembrane protein that functions as a broad post-translational stabilizer of cell-surface and signaling proteins by binding them in recycling endosomes and diverting them from ubiquitin-mediated degradation, with central roles in immune checkpoint control, receptor trafficking, and tumor biology (PMID:28813417, PMID:28813410). Its founding and best-defined function is stabilization of PD-L1: CMTM6 (and its closest family member CMTM4) associates with PD-L1 at the plasma membrane and in recycling endosomes, reduces PD-L1 ubiquitination, extends its half-life without altering CD274 transcription, and thereby sustains tumor-cell suppression of T cells (PMID:28813417, PMID:28813410). CMTM6 acts as a shared, rate-limiting chaperone for which client proteins compete: CD58 and PD-L1 compete for CMTM6 binding, so loss of one client frees CMTM6 to stabilize the other (PMID:37327789). Structurally, CMTM6 forms a membrane-bound complex with full-length PD-L1 that enhances PD-1 binding and delays PD-1/PD-L1 dissociation, and a CMTM6-targeting nanobody relieves T-cell immunosuppression and inhibits tumor growth in a CD8+ T-cell-dependent manner (PMID:36418428). Beyond PD-L1, CMTM6 stabilizes a wide range of clients by the same endosomal anti-degradation logic—EGFR via RAB11-positive recycling endosomes (PMID:40521789), Glut1 in a Rab11-dependent complex to support glycolysis and metastasis (PMID:39218981), Nectin-2/PVRL2 via RAB14/RAB11 trafficking to restrain NK-cell attack (PMID:41840509), β-catenin (PMID:38101607), the cell-cycle inhibitor p21 (PMID:35304440), vimentin (PMID:33757532), and TAK1 (PMID:41836582)—linking it to receptor signaling, metabolic reprogramming, epithelial-mesenchymal transition, and inflammatory pathways. CMTM6 itself is regulated post-transcriptionally and by partner binding: HuR stabilizes CMTM6 mRNA through AU-rich elements in its 3'UTR (PMID:33649535), while MAVS (PMID:41469142) and the receptor tyrosine kinase FLT3, via a transmembrane-domain interaction, shield CMTM6 protein from degradation (PMID:41043134). Loss of CMTM6 can trigger DNA damage response, senescence, and a SASP that recruits T cells (PMID:35024247, PMID:41469142). CMTM6 also has non-tumor physiological roles, including maintaining adaxonal Schwann cell membrane structure and constraining axonal diameter (PMID:32908139), suppressing ocular surface inflammation via NF-κB p65 (PMID:38165704), and, in mice but not humans, negatively regulating surface FAS to limit FAS-ligand cytotoxicity (PMID:41634378).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2017 High

    Established the founding function of CMTM6 by answering how PD-L1 protein is maintained at the cell surface independent of transcription, identifying CMTM6 as the rate-limiting stabilizer of the immune checkpoint.

    Evidence Genome-wide CRISPR and haploid genetic screens, Co-IP, ubiquitination and half-life assays, quantitative membrane proteomics, and T-cell suppression assays in two independent studies

    PMID:28813410 PMID:28813417

    Open questions at the time
    • Did not resolve the E3 ligase machinery from which CMTM6 protects PD-L1
    • Mechanism of the CMTM6-PD-L1 transmembrane interaction not structurally defined
  2. 2020 High

    Revealed a physiological, non-immune role for CMTM6 by localizing it to the adaxonal Schwann cell membrane and showing it constrains axonal diameter, demonstrating function beyond checkpoint biology.

    Evidence Label-free proteomics, STED and cryo-immuno EM, and Schwann cell-specific conditional knockout mice with electrophysiology

    PMID:32908139

    Open questions at the time
    • Molecular client mediating axonal diameter control not identified
    • Connection to the endosomal stabilization mechanism not established in this tissue
  3. 2020 Medium

    Extended CMTM6 into the tumor microenvironment as a transferable factor, showing exosomal CMTM6 polarizes macrophages and that CMTM6 promotes OSCC via NRP1 interaction.

    Evidence Exosome isolation with macrophage co-culture and 4NQO mouse model; Co-IP and gain/loss-of-function invasion assays

    PMID:32642284 PMID:33104837

    Open questions at the time
    • NRP1-dependent CMTM6 degradation mechanism not dissected
    • Exosomal ERK1/2 activation mechanism downstream of CMTM6 unresolved
  4. 2021 Medium

    Generalized the stabilization mechanism beyond surface receptors by showing CMTM6 protects intracellular and cytoskeletal clients (p21, vimentin, ENO-1) from degradation, linking it to cell-cycle, EMT, and metabolic/Wnt signaling.

    Evidence Co-IP, ubiquitination assays, cell cycle analysis, proteomics, and xenograft models across HCC and OSCC

    PMID:33434185 PMID:33757532 PMID:35304440

    Open questions at the time
    • Whether these are direct binding clients or indirect effects not fully separated
    • Specificity determinants for the diverse client set unknown
  5. 2021 Medium

    Identified upstream regulation of CMTM6 itself, answering how its abundance is set, via HuR-mediated mRNA stabilization and EMT/SNAI1-driven co-induction with CMTM7.

    Evidence RNA-IP, mRNA stability assays, HuR inhibitor, and SNAI1-inducible EMT model with dual siRNA knockdown

    PMID:33649535 PMID:33803139

    Open questions at the time
    • Relative contribution of transcriptional vs post-transcriptional control across tissues unknown
    • Functional redundancy boundary between CMTM6 and CMTM7 not mapped
  6. 2022 High

    Provided structural and biochemical mechanism by reconstituting the membrane CMTM6-PD-L1 complex and showing CMTM6 directly enhances PD-1/PD-L1 affinity, and demonstrated loss-of-CMTM6 triggers DDR-driven senescence.

    Evidence In vitro reconstitution with binding kinetics and anti-CMTM6 nanobody in CT26 mice; CMTM6 depletion with DNA damage and micronucleus assays in ccRCC

    PMID:35024247 PMID:36418428

    Open questions at the time
    • High-resolution structure of the complex not determined
    • Mechanism linking CMTM6 loss to DNA damage response not defined
  7. 2023 High

    Defined CMTM6 as a shared limiting chaperone subject to client competition, and extended its trafficking-based stabilization to EGFR and β-catenin with therapeutic targeting.

    Evidence CRISPR screen, proteomics, humanized mouse and PDX models; Co-IP, RAB11 co-localization imaging, ubiquitination assays, and CMTM6-targeting nanobody

    PMID:31771985 PMID:37327789 PMID:38101607 PMID:40521789

    Open questions at the time
    • Hierarchy of client affinities not quantified
    • How a single protein selects among competing clients spatially unresolved
  8. 2024 Medium

    Broadened the trafficking mechanism to a metabolic transporter and to transcription/epigenetic feedback, with Glut1 stabilization via a Rab11 complex and an EP300-CMTM6-IGF2BP1 loop.

    Evidence Endosomal fractionation, Co-IP, glycolysis assays, metastasis models; ChIP-seq, ubiquitination assay, RIP, and PDX models

    PMID:39218981 PMID:39488785

    Open questions at the time
    • Direct vs scaffold role of CMTM6 within the Rab11 transport complex unclear
    • Whether IGF2BP1 stabilization is direct binding not established
  9. 2024 Medium

    Established CMTM6 as a homeostatic anti-inflammatory factor at epithelial barriers, showing it suppresses NF-κB p65 to maintain corneal epithelial integrity.

    Evidence Cmtm6 knockout mice, NF-κB inhibitor rescue, barrier (ECIS) and ZO-1 immunofluorescence assays

    PMID:38165704

    Open questions at the time
    • Molecular client linking CMTM6 to NF-κB suppression not identified
    • Whether this involves the endosomal stabilization mechanism unknown
  10. 2025 Medium

    Identified partners that stabilize CMTM6 protein itself, with MAVS shielding CMTM6 from lysosomal degradation and the MAVS-CMTM6 axis governing mitochondrial stress and antitumor immunity.

    Evidence Co-IP, mass spectrometry, MAVS-deficient mouse models, ROS scavenging, and CD8+ T-cell depletion

    PMID:41469142

    Open questions at the time
    • Subcellular site of MAVS-CMTM6 interaction not pinned down
    • How CMTM6 loss provokes mitochondrial dysfunction mechanistically unresolved
  11. 2026 High

    Defined transmembrane-domain-mediated partner control and species-specific clients, with FLT3 stabilizing CMTM6 in AML, CMTM6 stabilizing Nectin-2 and TAK1, and a mouse-specific FAS interaction.

    Evidence Transmembrane-domain Co-IP, allogeneic HCT and CIA mouse models, CHX chase, mass spectrometry interactome, and human-mouse domain mutagenesis

    PMID:41043134 PMID:41634378 PMID:41836582 PMID:41840509

    Open questions at the time
    • Structural basis of transmembrane-domain recognition across partners not resolved
    • General rules predicting which receptors CMTM6 stabilizes vs which stabilize CMTM6 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what structural and biochemical features determine CMTM6 client selectivity and the directionality of stabilization, and which ubiquitin ligases CMTM6 antagonizes for each client.
  • No unifying structural model of CMTM6 client recognition
  • Cognate E3 ligases for most clients unidentified
  • Quantitative client-competition hierarchy not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005768 endosome 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3
Partners
CD274CD58CTNNB1EGFRFLT3MAVSPVRL2SLC2A1
Complex memberships
CMTM6-Glut1-Rab11 complexCMTM6-PD-L1 complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 CMTM6 binds PD-L1 at the plasma membrane and in recycling endosomes, preventing lysosome-mediated degradation of PD-L1 without affecting its transcription or maturation. CMTM6 depletion selectively reduces PD-L1 surface expression while leaving MHC class I unaffected, and reduces T-cell suppression in vitro and in vivo. Genome-wide CRISPR-Cas9 screen, co-immunoprecipitation, quantitative plasma membrane proteomics, co-localization by imaging, xenograft mouse models, T-cell suppression assays Nature High 28813417
2017 CMTM6 (and its closest family member CMTM4, but not other CMTM members) associates with PD-L1 protein at the cell surface, reduces PD-L1 ubiquitination, and increases PD-L1 protein half-life without affecting CD274 transcription, thereby enhancing the ability of PD-L1-expressing tumor cells to inhibit T cells. This function was confirmed by haploid genetic modifier screen and genetic complementation. Haploid genetic screen, haploid genetic modifier screen, genetic complementation, co-immunoprecipitation, ubiquitination assays, protein half-life measurements, T-cell inhibition co-culture assays Nature High 28813410
2023 CMTM6 is critical for CD58 protein stability in addition to PD-L1. Competition between CD58 and PD-L1 for CMTM6 binding determines their rate of endosomal recycling over lysosomal degradation. Loss of CD58 leads to increased PD-L1 protein stabilization via freed CMTM6. CRISPR-Cas9 screen, proteomics, patient-derived co-cultures, humanized mouse models, single-cell RNA-sequencing, validation experiments Cancer cell High 37327789
2021 CMTM6 physically interacts with p21 and prevents its ubiquitination mediated by SCFSKP2, CRL4CDT2, and APC/CCDC20 E3 ligase complexes in a cell-cycle-independent manner, thereby stabilizing p21 protein and leading to inactivation of the pRB/E2F pathway and G1/S phase arrest in hepatocellular carcinoma cells. Co-immunoprecipitation, ubiquitination assays, in vitro and in vivo proliferation assays, cell cycle analysis, western blotting, xenograft models Cell death & disease High 35304440
2021 CMTM6 physically interacts with and stabilizes vimentin, thereby promoting epithelial-mesenchymal transition (EMT) and increasing proliferation, migration, and invasion of hepatocellular carcinoma cells. Co-immunoprecipitation, immunofluorescence, shRNA knockdown, overexpression, wound-healing assay, Matrigel invasion assay, xenograft model Journal of translational medicine Medium 33757532
2021 CMTM6 interaction with membrane-bound Enolase-1 (ENO-1) stabilizes ENO-1 expression, leading to activation of Wnt signaling mediated by AKT–glycogen synthase kinase-3β (GSK3β), thereby driving cisplatin resistance in oral squamous cell carcinoma. Global proteome profiling, stable knockdown and overexpression, patient-derived cell xenograft, transcriptome analysis, co-immunoprecipitation/interaction assays JCI insight Medium 33434185
2022 CMTM6 regulates ribosome biogenesis by inducing C-Myc expression (which promotes RNA polymerase I-mediated rDNA transcription) and by regulating AKT-mTORC1-dependent ribosome biogenesis and protein synthesis in cisplatin-resistant oral squamous cell carcinoma cells. RNA sequencing, CMTM6 knockdown/overexpression, rRNA transcription assays, nucleolar structure analysis, nude mice and zebrafish xenograft experiments FASEB journal Medium 36165231
2020 CMTM6 is specifically localized to the adaxonal Schwann cell membrane (identified by label-free proteomics, STED-microscopy, and cryo-immuno electron-microscopy). Disruption of Cmtm6 expression in Schwann cells causes a substantial increase in axonal diameters without impairing myelin biogenesis, radial sorting, or axonal integrity, correlating with accelerated sensory nerve conduction and perturbed motor performance. Label-free proteomics, STED-microscopy, cryo-immuno electron-microscopy, conditional Schwann cell-specific knockout mice, electrophysiology Nature communications High 32908139
2020 OSCC cell-secreted exosomal CMTM6 is transferred to macrophages and promotes M2-like macrophage polarization through activating ERK1/2 signaling. Ultracentrifugation-derived exosomes, qPCR, western blot, co-culture macrophage polarization assays, 4NQO-induced OSCC mouse model Cancer immunology, immunotherapy : CII Medium 33104837
2020 CMTM6 promotes cell proliferation and invasion in oral squamous cell carcinoma by physically interacting with Neuropilin-1 (NRP1). NRP1 silencing abrogates CMTM6-induced tumorigenesis. NRP1 is involved in the degradation process of CMTM6 (silencing NRP1 decreased CMTM6 stability). Co-immunoprecipitation, gain- and loss-of-function assays, wound-healing, Matrigel invasion assay, immunofluorescence American journal of cancer research Medium 32642284
2021 HuR RNA-binding protein stabilizes CMTM6 mRNA via direct association with AU-rich elements (AREs) in its 3'UTR, thereby upregulating CMTM6 and consequently increasing cell surface PD-L1 levels in cancer cells. HuR inhibition (MS-444) reduces CMTM6/PD-L1 and relieves T-cell immunosuppression. RNA immunoprecipitation, mRNA stability assays, HuR overexpression/knockdown, HuR inhibitor (MS-444), T-cell co-culture assays, in vivo allograft model Oncogene Medium 33649535
2023 CMTM6 is physically associated with EGFR and co-localizes with EGFR in RAB11-positive recycling endosomes, preventing EGFR from lysosome-mediated degradation in NSCLC cells. A CMTM6-targeting nanobody blocks the CMTM6-EGFR interaction, reduces EGFR protein levels, and inhibits TKI-resistant NSCLC growth in vitro and in vivo. Co-immunoprecipitation, co-localization imaging, shRNA knockdown, nanobody development, cell-line-derived and patient-derived xenograft models Advanced science Medium 40521789
2023 CMTM6 promotes HCC cell proliferation by physically interacting with β-catenin and stabilizing it by preventing its ubiquitination, thereby activating the β-catenin/Wnt pathway. Cmtm6 knockout mice showed inhibited HCC formation in DEN and DEN/CCl4-induced primary liver cancer models. Co-immunoprecipitation, ubiquitination assay, Cmtm6 knockout mice (primary liver cancer models), HCC cell line overexpression/knockdown Cancer letters Medium 38101607
2024 CMTM6 forms a complex with Glut1 and Rab11 in endosomes of colorectal cancer cells, and this complex is required for Rab11-dependent transport of Glut1 to the plasma membrane, protecting Glut1 from lysosomal degradation and thereby enabling the Warburg effect and supporting liver metastasis. shRNA knockdown, co-immunoprecipitation, endosomal fractionation, glucose uptake/glycolysis assays, subcutaneous and liver metastasis mouse models, multiomics (transcriptomics, proteomics) Experimental & molecular medicine Medium 39218981
2022 Loss of CMTM6 in clear cell renal cell carcinoma triggers aberrant activation of the DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, leading to cellular senescence with upregulation of chemokines and cytokines (SASP), and increased CD4+ and CD8+ T-cell infiltration. CMTM6 depletion in vitro and in vivo (xenograft, syngeneic graft mouse models), DNA damage assays, cell cycle analysis, micronucleus detection, cytokine profiling, flow cytometry Oncoimmunology Medium 35024247
2024 EP300-mediated H3K27ac modification drives transcriptional activation of CMTM6 in pancreatic ductal adenocarcinoma. CMTM6, in turn, maintains IGF2BP1 expression by preventing its ubiquitination. IGF2BP1 (as an m6A reader) stabilizes EP300 and MYC mRNAs, forming a positive feedback loop (EP300-CMTM6-IGF2BP1) that enhances tumor stemness and gemcitabine resistance. Gemcitabine-resistant PDAC cell lines and PDX models, RNA sequencing, multi-omics, ChIP-seq (H3K27ac), ubiquitination assay, IGF2BP1 RIP, EP300 inhibitor (inobrodib) combination experiments Advanced science Medium 39488785
2022 A stable membrane-bound full-length CMTM6-PD-L1 complex was assembled using LMNG detergent and amphipol A8-35. Biochemical analysis showed that CMTM6 greatly enhances PD-1 binding to PD-L1 and delays dissociation of PD-1/PD-L1, thereby affecting immunosuppressive and anti-apoptotic signaling. An anti-CMTM6 nanobody (1A5) derived from this complex decreased T-cell immunosuppression and inhibited tumor growth in CT26 tumor-bearing mice in a CD8+ T-cell-dependent manner. In vitro reconstitution of CMTM6-PD-L1 complex, binding kinetics (SPR/BLI-type), camel immune repertoire nanobody generation, T-cell co-culture assays, CT26 syngeneic tumor model Acta pharmacologica Sinica High 36418428
2026 FLT3 physically interacts with CMTM6 within their transmembrane domains (in a phosphorylation-independent manner) and enhances CMTM6 protein stability in AML cells, increasing PD-L1 surface expression. FLT3 inhibition reduces CMTM6 and PD-L1 expression. Cmtm6-deficient FLT3-ITD+ leukemia cells showed prolonged survival, reduced leukemia burden, and enhanced T-cell effector function in allogeneic hematopoietic cell transplantation mouse models. Co-immunoprecipitation (transmembrane domain interaction), FLT3 inhibition, Cmtm6 knockout in FLT3-ITD+ leukemia cells, three allogeneic HCT mouse models, flow cytometry (T-cell exhaustion markers), primary patient AML cell validation Cancer research High 41043134
2026 Mouse CMTM6 strongly associates with the death receptor FAS (identified by mass spectrometry) and negatively regulates FAS surface expression in mice. CMTM6 deletion increases FAS plasma membrane localization and sensitizes murine cells to FAS ligand-induced cytotoxicity. This interaction is absent in human cells due to differences in three amino acids at the boundary of the FAS extracellular and transmembrane domains. Mass spectrometry interactome, co-immunoprecipitation, FAS surface expression by flow cytometry, CMTM6 deletion, FAS ligand cytotoxicity assays, human-mouse domain comparison and mutagenesis EMBO reports High 41634378
2021 In ANCA-associated vasculitis (AAV), monocytes have reduced CMTM6 expression, leading to enhanced lysosomal degradation of PD-L1, lower PD-L1 surface expression, and increased T-cell stimulatory capacity. Inhibiting lysosomal function corrected this phenotype by increasing PD-L1. In vitro co-culture of patient monocytes, surface PD-L1 measurement, lysosomal inhibitor experiments, CD4+ T-cell activation/proliferation assays Frontiers in immunology Medium 34108971
2025 MAVS co-localizes with and stabilizes CMTM6, shielding it from lysosomal degradation. Disruption of the MAVS-CMTM6 axis provokes mitochondrial dysfunction and ROS accumulation, leading to senescence and a SASP marked by CCL3, which recruits CD8+ T cells for antitumor immunity in renal carcinoma. Co-immunoprecipitation, mass spectrometry, co-localization imaging, MAVS-deficient mouse models, ROS scavenging (NAC), CD8+ T-cell depletion, flow cytometry, PD-1 blockade combination Journal for immunotherapy of cancer Medium 41469142
2024 CMTM6 inhibits ocular surface inflammation and maintains corneal epithelial barrier function via suppression of the NF-κB p65 signaling pathway. CMTM6 knockout mice showed more severe dry eye disease, barrier disruption, and reduced ZO-1 expression. NF-κB p65 inhibition reversed the excessive inflammation caused by CMTM6 knockdown. Cmtm6 knockout mice, siRNA/shRNA knockdown, lentiviral overexpression, NF-κB p65 inhibitor (JSH-23), ECIS barrier assay, immunofluorescence (ZO-1), flow cytometry, cytometric bead array Investigative ophthalmology & visual science Medium 38165704
2026 CMTM6 interacts with Nectin-2 (PVRL2) via RAB14/RAB11-mediated endosomal trafficking, inhibiting Nectin-2 degradation through both lysosomal and proteasomal pathways. CMTM6 knockdown enhances NK cell infiltration into gastric tumors and suppresses tumor growth. Proteomic analysis, co-immunoprecipitation, cycloheximide chase assay, lysosomal/proteasomal inhibitors, animal models of gastric cancer, tumor tissue microarray BMC cancer Medium 41840509
2026 CMTM6 maintains TAK1 stability by inhibiting its ubiquitin-proteasome degradation in fibroblast-like synoviocytes (FLSs), thereby activating the TNF/TNFR pathway and downstream NF-κB/MAPK signaling and promoting synovial inflammation in rheumatoid arthritis. AAV-mediated Cmtm6 knockdown attenuated arthritis severity in collagen-induced arthritis mice. Co-immunoprecipitation, immunofluorescence, ubiquitination assay, cycloheximide (CHX) assay, RNA-sequencing, AAV-shCmtm6 treatment in CIA mice, micro-CT and histology Journal of orthopaedic translation Medium 41836582
2023 CMTM6 knockdown in HNSCC cells reduced nuclear β-catenin expression, inhibited stem cell-like properties, TGFβ-induced EMT, and cell proliferation. CMTM6 silencing also decreased PD-L1, delayed tumor growth in vivo, and increased CD8+ and CD4+ T-cell infiltration while reducing exhausted T-cell populations. shRNA knockdown, western blotting, flow cytometry, T-cell infiltration analysis in syngeneic SCC7 tumor model Cancer immunology research Medium 31771985
2021 CMTM6 and CMTM7 are co-induced with EMT (driven by SNAI1) in breast cancer cells and together regulate surface PD-L1 expression. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression more than either alone in mesenchymal breast cancer cells. SNAI1-inducible EMT model in MCF-7 cells, siRNA knockdown of CMTM6 and/or CMTM7, flow cytometry for surface PD-L1 Cancers Medium 33803139

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. Nature 762 28813417
2017 Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 575 28813410
2019 Targeting CMTM6 Suppresses Stem Cell-Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma. Cancer immunology research 111 31771985
2020 OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway. Cancer immunology, immunotherapy : CII 97 33104837
2023 The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity. Cancer cell 71 37327789
2021 CMTM6 drives cisplatin resistance by regulating Wnt signaling through the ENO-1/AKT/GSK3β axis. JCI insight 64 33434185
2019 Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non-Small Cell Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 52 31605795
2019 Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients. Oncoimmunology 50 31646074
2023 CMTM6 overexpression confers trastuzumab resistance in HER2-positive breast cancer. Molecular cancer 45 36627608
2018 Expression and Clinical Significance of CMTM6 in Hepatocellular Carcinoma. DNA and cell biology 45 30562063
2022 CMTM6 inhibits tumor growth and reverses chemoresistance by preventing ubiquitination of p21 in hepatocellular carcinoma. Cell death & disease 41 35304440
2021 HuR up-regulates cell surface PD-L1 via stabilizing CMTM6 transcript in cancer. Oncogene 38 33649535
2023 Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis. Biology direct 36 37592296
2021 CMTM6 promotes migration, invasion, and EMT by interacting with and stabilizing vimentin in hepatocellular carcinoma cells. Journal of translational medicine 36 33757532
2020 Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression. International immunopharmacology 35 32278132
2020 CMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves. Nature communications 32 32908139
2023 circ-0000512 inhibits PD-L1 ubiquitination through sponging miR-622/CMTM6 axis to promote triple-negative breast cancer and immune escape. Journal for immunotherapy of cancer 29 37349124
2022 Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity. Oncoimmunology 29 35024247
2020 CMTM6 promotes cell proliferation and invasion in oral squamous cell carcinoma by interacting with NRP1. American journal of cancer research 28 32642284
2021 Epithelial to Mesenchymal Transition Regulates Surface PD-L1 via CMTM6 and CMTM7 Induction in Breast Cancer. Cancers 27 33803139
2021 CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer. Cancer immunology, immunotherapy : CII 25 33818637
2019 CMTM6, the newly identified PD-L1 regulator, correlates with PD-L1 expression in lung cancers. Biochemistry and biophysics reports 22 31646201
2020 Quantitative analysis of CMTM6 expression in tumor microenvironment in metastatic melanoma and association with outcome on immunotherapy. Oncoimmunology 21 33457084
2021 CMTM6-Deficient Monocytes in ANCA-Associated Vasculitis Fail to Present the Immune Checkpoint PD-L1. Frontiers in immunology 20 34108971
2021 High membrane expression of CMTM6 in hepatocellular carcinoma is associated with tumor recurrence. Cancer science 19 34080242
2020 CMTM6 is positively correlated with PD-L1 expression and immune cells infiltration in lung squamous carcinoma. International immunopharmacology 18 32866782
2022 CMTM6 as a master regulator of PD-L1. Cancer immunology, immunotherapy : CII 16 35294592
2022 CMTM6 attenuates cisplatin-induced cell death in OSCC by regulating AKT/c-Myc-driven ribosome biogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 36165231
2023 CMTM6 promotes hepatocellular carcinoma progression through stabilizing β-catenin. Cancer letters 13 38101607
2021 Co-Expression with Membrane CMTM6/4 on Tumor Epithelium Enhances the Prediction Value of PD-L1 on Anti-PD-1/L1 Therapeutic Efficacy in Gastric Adenocarcinoma. Cancers 13 34680324
2020 Expression Analysis of Canine CMTM6 and CMTM4 as Potential Regulators of the PD-L1 Protein in Canine Cancers. Frontiers in veterinary science 13 32596272
2021 CMTM6 and PD-1/PD-L1 overexpression is associated with the clinical characteristics of malignancy in oral squamous cell carcinoma. Oral surgery, oral medicine, oral pathology and oral radiology 12 34034998
2024 CMTM6 mediates the Warburg effect and promotes the liver metastasis of colorectal cancer. Experimental & molecular medicine 11 39218981
2024 Epigenetic Activation of the CMTM6-IGF2BP1-EP300 Positive Feedback Loop Drives Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 39488785
2021 CMTM6, a potential immunotherapy target. Journal of cancer research and clinical oncology 10 34783871
2020 Expression and Clinical Significance of CMTM6 in Nonsmall Cell Lung Cancer. DNA and cell biology 10 33090010
2023 Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner. Cancer immunology research 9 36484740
2022 CMTM6 knockdown prevents glioma progression by inactivating the mTOR pathway. Annals of translational medicine 9 35280358
2021 The association between the expression of PD-L1 and CMTM6 in undifferentiated pleomorphic sarcoma. Journal of cancer research and clinical oncology 9 33811537
2022 CMTM6 and CMTM7: New leads for PD-L1 regulation in breast cancer cells undergoing EMT. Journal of cellular biochemistry 7 35575054
2024 Transmembrane Protein CMTM6 Alleviates Ocular Inflammatory Response and Improves Corneal Epithelial Barrier Function in Experimental Dry Eye. Investigative ophthalmology & visual science 6 38165704
2022 Construction of stable membranal CMTM6-PD-L1 full-length complex to evaluate the PD-1/PD-L1-CMTM6 interaction and develop anti-tumor anti-CMTM6 nanobody. Acta pharmacologica Sinica 6 36418428
2021 Impact of CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) expression in gastric cancer. The journal of medical investigation : JMI 6 34759159
2025 Oncogenic CMTM6 drives M2a macrophages formation and fuels cervical cancer progression. Frontiers in immunology 5 40761779
2024 Autophagy-related CMTM6 promotes glioblastoma progression by activating Wnt/β-catenin pathway and acts as an onco-immunological biomarker. The journal of gene medicine 5 38686653
2023 CMTM6 recruits T cells within the endocervical adenocarcinoma microenvironment and suppresses cell proliferation via the p53 pathway. Journal of medical virology 5 36815510
2023 Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer. Medicine 5 38115316
2022 The predictive value and correlation of β-catenin, CMTM6, and PD-L1 expression in colorectal cancer. Neoplasma 5 35293763
2022 CMTM6 as a candidate risk gene for cervical cancer: Comprehensive bioinformatics study. Frontiers in molecular biosciences 5 36589225
2020 Schwann-cell-derived CMTM6 restricts radial axonal growth. Nature communications 5 33028828
2026 CMTM6 promotes synovial proliferation and macrophage polarization by preventing ubiquitination of TAK1 in rheumatoid arthritis. Journal of orthopaedic translation 4 41836582
2024 circUBR5 promotes ribosome biogenesis and induces docetaxel resistance in triple-negative breast cancer cell lines via the miR-340-5p/CMTM6/c-MYC axis. Neoplasia (New York, N.Y.) 4 39672097
2023 From patient tissue correlates to molecular mechanisms of cancer immune evasion: the emerging role of CD58 and PD-L1 co-regulation via CMTM6. Genes and immunity 4 38082156
2022 CMTM6: increased circulating level and up-regulated expression in labial salivary glands in patients with primary Sjogren's syndrome. Clinical and experimental immunology 4 35020842
2022 Expression and Clinical Significance of CMTM6 and PD-L1 in Triple-Negative Breast Cancer. BioMed research international 4 35845949
2025 A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40521789
2025 MAVS/CMTM6 axis couples mitochondrial homeostasis to immunogenic senescence via CCL3-driven T-cell recruitment in renal carcinoma. Journal for immunotherapy of cancer 3 41469142
2025 CMTM6 drives glioblastoma progression by promoting M2 polarization and suppressing antigen presentation in microglia/macrophages. European journal of medical research 2 41139792
2025 [Effect of CMTM6 on PD-L1 in Helicobacter pylori infected gastric epithelial cells]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 1 40219552
2024 Corrigendum: CMTM6 as a candidate risk gene for cervical cancer: comprehensive bioinformatics study. Frontiers in molecular biosciences 1 39108342
2024 New Advances in the Study of CMTM6, a Focus on Its Novel Non-Canonical Cellular Locations, and Functions beyond Its Role as a PD-L1 Stabilizer. Cancers 1 39335098
2024 CMTM6 status predicts survival in head and neck squamous cell carcinoma and correlates with PD-L1 expression. Discover oncology 1 39630300
2024 CMTM6 promotes hepatocellular carcinoma invasion and metastasis and tumor-associated neutrophil immunoinfiltration through the Wnt/β-catenin pathway. European journal of medical research 1 39696705
2023 CMTM6 is highly expressed in lung adenocarcinoma and can be used as a biomarker of a poor diagnosis. PeerJ 1 36643629
2023 CMTM6 as a potential therapy target is associated with immunological tumor microenvironment and can promote migration and invasion in pancreatic adenocarcinoma. Functional & integrative genomics 1 37726578
2026 FLT3-ITD Induces CMTM6 and Enhances Immune Escape in Acute Myeloid Leukemia. Cancer research 0 41043134
2026 CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans. EMBO reports 0 41634378
2026 CMTM6-Silencing Microbial Immunotherapy Reprograms PDAC Tumors and Restores T-cell Function. bioRxiv : the preprint server for biology 0 41659641
2026 Regulation of natural killer cell infiltration and tumor progression by CMTM6 in gastric cancer. BMC cancer 0 41840509
2026 CMTM6 promotes radioresistance in hepatocellular carcinoma via EMT induction and synergistic interaction with VEGFA. Acta biochimica et biophysica Sinica 0 42178284
2025 Retraction: CMTM6 as a candidate risk gene for cervical cancer: comprehensive bioinformatics study. Frontiers in molecular biosciences 0 41113856
2025 Retraction: Corrigendum: CMTM6 as a candidate risk gene for cervical cancer: comprehensive bioinformatics study. Frontiers in molecular biosciences 0 41122241
2025 Targeting PD-L1-CMTM6 interactions in myeloid cells triggers PD-L1 degradation and enhances cytotoxic T-cell expansion. Journal for immunotherapy of cancer 0 41151837
2025 CMTM6: a potential biomarker in non-small cell lung carcinoma. Polish journal of pathology : official journal of the Polish Society of Pathologists 0 41910081
2023 PD-L1 and CD58 co-regulated by CMTM6 play yin and yang to shape anti-tumor immunity. Cancer cell 0 37683640

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