Affinage

LGALS1

Galectin-1 · UniProt P09382

Length
135 aa
Mass
14.7 kDa
Annotated
2026-06-10
23 papers in source corpus 11 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LGALS1 (Galectin-1) is a secreted lectin that functions as a central driver of tumor immune evasion and pro-tumorigenic signaling across multiple cancers (PMID:42230983, PMID:30613962). Tumor- and fibroblast-derived LGALS1 reshapes the immune microenvironment, suppressing CD8+ T cell and NK cell function and reducing M2 macrophage and myeloid-derived suppressor cell populations upon its loss (PMID:30613962, PMID:38965225). Mechanistically, tumor-secreted LGALS1 binds with high affinity to CD276 (B7-H3) on endothelial cells through N-linked glycosylation at N433 in the CD276 D4 domain, activating MAP4-dependent PI3K/AKT signaling to promote angiogenesis and bladder cancer progression (PMID:42230983). In addition, LGALS1 acts as an upstream activator of a p38 MAPK/MMP-9 axis that drives epithelial-mesenchymal transition and metastasis (PMID:30159048), and in cancer-associated fibroblasts it promotes tumor cell proliferation and migration by upregulating CCR2, ADAM15, and β-integrin (PMID:38862197). LGALS1 protein abundance is controlled post-translationally: DUSP22 binds and dephosphorylates LGALS1 at Ser8 and Thr58, triggering its degradation and relieving LGALS1-mediated immunosuppression (PMID:41611244). Its expression is further regulated through miRNA targeting, including direct binding by miR-22-3p (PMID:36224027), and a CAF-derived miR-181b-5p/SEC24C/STING/YY1 axis that de-represses LGALS1 transcription (PMID:41713839). LGALS1 also confers a pro-survival, lipid-metabolism-linked phenotype in acute myeloid leukemia (PMID:32590026, PMID:38965225).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2018 Medium

    Established LGALS1 as a functional upstream driver of metastasis rather than a passive marker, by placing it at the head of a defined signaling axis.

    Evidence siRNA knockdown in invasive oral cancer cells with migration/invasion assays, an in vivo metastasis model, and Western blot for p38 MAPK and MMP-9

    PMID:30159048

    Open questions at the time
    • Does not show direct molecular binding linking LGALS1 to p38 activation
    • Mechanism of how a secreted lectin engages intracellular p38 signaling not resolved
  2. 2019 Medium

    Showed LGALS1 controls the myeloid arm of the immunosuppressive tumor microenvironment, defining it as a regulator of M2 macrophage and MDSC polarization.

    Evidence LGALS1 knockdown in vitro and in vivo in glioblastoma with flow cytometry for immune populations and cytokine measurement

    PMID:30613962

    Open questions at the time
    • Receptor mediating myeloid polarization not identified
    • Cannot distinguish secreted vs intracellular contributions
  3. 2020 Medium

    Demonstrated a cell-autonomous pro-survival role for LGALS1 in leukemia, linking it to apoptotic threshold and therapeutic sensitivity.

    Evidence shRNA knockdown in AML cell lines with ABT-737 sensitization and survival readout in a murine OCI-AML3 xenograft, plus RNASeq

    PMID:32590026

    Open questions at the time
    • Molecular link to BCL2-family apoptotic machinery not defined
    • Single lab
  4. 2022 Medium

    Identified upstream transcriptional control of LGALS1 by miR-22-3p, connecting its expression level to EMT regulation in melanoma.

    Evidence Dual luciferase reporter assay confirming direct mRNA binding, miR-22-3p overexpression with EMT marker Western blots

    PMID:36224027

    Open questions at the time
    • Does not establish LGALS1's own downstream effector mechanism in melanoma
    • In vivo relevance not tested
  5. 2022 Low

    Proposed an intracellular, non-lectin function for LGALS1 as an RNA-binding protein controlling alternative splicing.

    Evidence siRNA knockdown plus RNA-seq with RT-qPCR and overexpression rescue in NSCLC A549 cells

    PMID:37341175

    Open questions at the time
    • No direct RBP binding assay (CLIP/EMSA) confirming physical RNA interaction
    • Splicing targets validated only at expression level
  6. 2023 Medium

    Defined a stromal source of LGALS1 in cancer-associated fibroblasts and its downstream effectors driving tumor cell invasion.

    Evidence scRNA-seq identification with siRNA knockdown in CAFs, co-culture invasion assays, and in vivo tumor formation in cholangiocarcinoma

    PMID:38862197

    Open questions at the time
    • Direct mechanism by which LGALS1 induces CCR2/ADAM15/β-integrin not established
    • Receptor on tumor cells not identified
  7. 2024 Medium

    Connected LGALS1 to fatty acid metabolism and immune evasion in leukemia stem cells, extending its role beyond signaling to metabolic regulation.

    Evidence LGALS1 knockdown in vitro and in vivo with flow cytometry for CD8+ T/NK cells and lipid accumulation assays

    PMID:38965225

    Open questions at the time
    • Mechanistic link between LGALS1 and lipid metabolism not defined
    • Secreted vs intracellular role unresolved
  8. 2024 Low

    Implicated LGALS1 as an activator of PI3K/AKT signaling in a non-cancer fibrotic context.

    Evidence LGALS1 overexpression in TCMK-1 cells with PI3K/AKT phosphorylation Western blots in a TGF-β fibrosis model

    PMID:38967135

    Open questions at the time
    • Single overexpression experiment without loss-of-function or mutagenesis
    • No direct interaction defining how LGALS1 engages PI3K/AKT
  9. 2026 High

    Resolved a post-translational mechanism controlling LGALS1 stability, showing phosphorylation-state-dependent degradation governs its immunosuppressive output.

    Evidence Mass spectrometry, reciprocal co-IP, phosphomimetic mutagenesis of Ser8/Thr58, and mouse models

    PMID:41611244

    Open questions at the time
    • Kinase that phosphorylates Ser8/Thr58 not identified
    • Degradation machinery (E3 ligase) not defined
  10. 2026 High

    Identified the endothelial receptor CD276 as a direct high-affinity LGALS1 partner and mapped the glycan-dependent interaction driving angiogenesis.

    Evidence Human proteome microarray, co-IP, glycosylation-site mutagenesis (N433), and Cd276-/- and Lgals1-/- mouse models in bladder cancer

    PMID:42230983

    Open questions at the time
    • Whether CD276 binding mediates LGALS1's immune effects vs angiogenesis alone not separated
    • MAP4-to-PI3K/AKT coupling mechanism not detailed
  11. 2026 Medium

    Placed LGALS1 within a CAF-to-tumor transcriptional circuit that de-represses its expression and enables T cell suppression.

    Evidence miR-181b-5p/SEC24C/STING/YY1 pathway dissection with reporter and expression assays, T cell suppression assays, and mouse models in pancreatic cancer

    PMID:41713839

    Open questions at the time
    • Role of SUSD2 in LGALS1 secretion mechanistically thin
    • Many steps in one model not independently validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor(s) and molecular mechanism by which secreted LGALS1 suppresses CD8+ T and NK cells, and how its secreted lectin activity connects to the intracellular signaling and RNA-binding functions ascribed to it, remain unresolved.
  • No defined T cell receptor for LGALS1 in the corpus
  • Intracellular vs extracellular functional separation untested
  • No structural model of LGALS1 in complex with any partner

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2
Partners
CD276DUSP22

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2026 DUSP22 binds to LGALS1 and dephosphorylates it at Ser8 and Thr58 residues, leading to LGALS1 protein degradation and subsequent alleviation of LGALS1-mediated immunosuppression; this was confirmed by mass spectrometry, co-immunoprecipitation, and phosphomimetic mutant experiments. Mass spectrometry, co-immunoprecipitation, phosphomimetic mutagenesis, flow cytometry, mouse models Journal for immunotherapy of cancer High 41611244
2026 Tumor cell-secreted LGALS1 binds with high affinity to CD276 (B7-H3) on endothelial cells, with the interaction mediated by N-linked glycosylation at the N433 site within the D4 domain of CD276; this interaction activates MAP4-dependent PI3K/AKT signaling to promote angiogenesis and bladder cancer progression. Human proteome microarray, co-immunoprecipitation, glycosylation site mutagenesis, subcutaneous and orthotopic mouse models, Cd276−/− and Lgals1−/− mouse models Cell death and differentiation High 42230983
2018 LGALS1 knockdown in highly invasive oral cancer cells inactivates p38 MAPK phosphorylation, downregulates MMP-9, and inhibits epithelial-mesenchymal transition (EMT), establishing LGALS1 as an upstream regulator of the p38 MAPK/MMP-9/EMT axis in oral cancer metastasis. siRNA knockdown, in vitro migration/invasion assays, in vivo mouse metastasis model, western blot for p38 MAPK phosphorylation and MMP-9 Therapeutic advances in medical oncology Medium 30159048
2023 LGALS1+ fibroblasts promote proliferation and migration of intrahepatic cholangiocarcinoma cells by upregulating CCR2, ADAM15, and β-integrin expression; silencing LGALS1 in cancer-associated fibroblasts suppressed tumor cell migration and invasion in vitro and tumor formation in vivo. Single-cell RNA sequencing, siRNA knockdown in CAFs, in vitro co-culture migration/invasion assays, in vivo tumor formation model Journal of molecular cell biology Medium 38862197
2026 CAF-derived miR-181b-5p targets SEC24C in pancreatic cancer cells to inhibit STING phosphorylation, which blocks YY1 nuclear translocation and de-represses LGALS1 transcription; upregulated LGALS1 is then secreted via SUSD2 assistance to suppress CD8+ T cell function and induce apoptosis. In vitro T cell suppression assays, in vivo mouse models, pathway inhibition experiments, mechanistic reporter and expression assays Cancer letters Medium 41713839
2020 LGALS1 knockdown in AML cell lines sensitized them to BCL2 inhibitor ABT-737, and in vivo shRNA-mediated LGALS1 suppression in a murine OCI-AML3 xenograft model significantly prolonged survival, demonstrating a pro-survival function of LGALS1 in AML. shRNA knockdown, murine xenograft model, RNASeq gene expression profiling Biochimica et biophysica acta. Molecular cell research Medium 32590026
2019 Knockdown of LGALS1 in glioblastoma remodels the immunosuppressive microenvironment by downregulating M2 macrophages and myeloid-derived suppressor cells (MDSCs) and inhibiting immunosuppressive cytokines, placing LGALS1 as a regulator of myeloid cell polarization in the tumor microenvironment. LGALS1 knockdown in vitro and in vivo, flow cytometry for immune cell populations, cytokine measurement International journal of cancer Medium 30613962
2024 LGALS1 overexpression in kidney tubular TCMK-1 cells increased fibrosis markers and upregulated PI3K and AKT phosphorylation, establishing LGALS1 as an activator of the PI3K/AKT signaling pathway in renal fibrosis. LGALS1 overexpression in TCMK-1 cells, Western blot for PI3K/AKT phosphorylation, TGF-β-induced fibrosis model Renal failure Low 38967135
2024 LGALS1 repression in AML cells inhibited proliferation, enhanced apoptosis, decreased lipid accumulation, and curbed AML progression in vivo; LGALS1 repression also reduced CD8+ T and NK cell suppression in vivo, linking LGALS1 to fatty acid metabolism and immune evasion in leukemia stem cells. LGALS1 knockdown in vitro and in vivo, flow cytometry for immune cells, lipid accumulation assays Cell death & disease Medium 38965225
2022 LGALS1 silencing in NSCLC A549 cells altered alternative splicing of BCAP29, CSNKIE, and MDFIC and regulated expression of ELMO1, KCNJ2, and HSPA6, with LGALS1 overexpression rescuing these changes, identifying LGALS1 as an RNA-binding protein regulating alternative splicing in NSCLC. siRNA knockdown, RNA sequencing, RT-qPCR, LGALS1 overexpression rescue Advances in clinical and experimental medicine Low 37341175
2022 miR-22-3p directly binds to LGALS1 mRNA (confirmed by dual luciferase assay); overexpression of miR-22-3p in melanoma cells decreased LGALS1 expression, reduced VIM and SNAI2, increased CDH1, and inhibited EMT, establishing LGALS1 as a target of miR-22-3p-mediated EMT regulation in melanoma. Dual luciferase reporter assay, miR-22-3p overexpression, western blot for EMT markers, cell viability and apoptosis assays Frontiers in bioscience (Landmark edition) Medium 36224027
2026 In glioblastoma, TGFBR2 expression in mesenchymal glioma stem cells drives a 6-gene immunosuppressive Treg-like signature that includes LGALS1 (galectin-1), and TGFBR2 inhibition reversed this signature and restored CD4+ and CD8+ T cell function. Transgenic TGFBR2 expression, shRNA-based TGFBR2 inhibition, single-cell sequencing, T cell viability assays bioRxiv (preprint)preprint Low

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma. International journal of cancer 92 30613962
2022 NCAPG promotes the oncogenesis and progression of non-small cell lung cancer cells through upregulating LGALS1 expression. Molecular cancer 41 35180865
2015 Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9). Scientific reports 38 25687228
2018 Upregulation of LGALS1 is associated with oral cancer metastasis. Therapeutic advances in medical oncology 30 30159048
2020 LGALS1 acts as a pro-survival molecule in AML. Biochimica et biophysica acta. Molecular cell research 27 32590026
2019 Unraveling LGALS1 as a Potential Immune Checkpoint and a Predictor of the Response to Anti-PD1 Therapy in Clear Cell Renal Carcinoma. Pathology oncology research : POR 25 31428993
2023 Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma. EMBO molecular medicine 17 37791581
1993 Two members of the S-lac lectin gene family, LGALS1 and LGALS2, reside in close proximity on human chromosome 22q12-q13. Genomics 17 8449510
2024 A novel LGALS1-depended and immune-associated fatty acid metabolism risk model in acute myeloid leukemia stem cells. Cell death & disease 13 38965225
2022 Exosomal miR-22-3p from Mesenchymal Stem Cells Inhibits the Epithelial-Mesenchymal Transition (EMT) of Melanoma Cells by Regulating LGALS1. Frontiers in bioscience (Landmark edition) 12 36224027
2024 Screening of active components in Astragalus mongholicus Bunge and Panax notoginseng formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis. Renal failure 11 38967135
2022 Association between abnormal expression and methylation of LGALS1 in amyotrophic lateral sclerosis. Brain research 7 35872012
2024 Single-cell analysis defines LGALS1+ fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma. Journal of molecular cell biology 6 38862197
2015 Molecular characterization of the lgals1 gene in large scale loach Paramisgurnus dabryanus. Gene 6 26611526
2023 LGALS1 regulates cell adhesion to promote the progression of ovarian cancer. Oncology letters 5 37415637
2016 Different expression patterns of LGALS1 and LGALS3 in polycythemia vera, essential thrombocythemia and primary myelofibrosis. Journal of clinical pathology 3 27402956
2026 DUSP22 dephosphorylates LGALS1 to enhance T cell-driven antitumor immunity. Journal for immunotherapy of cancer 1 41611244
2024 RNA sequencing reveals the transcriptomic landscape and alternative splicing events induced by LGALS1 silencing in non-small cell lung cancer. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 1 37341175
2022 Genetic LGALS1 Variants Are Associated with Heterogeneity in Galectin-1 Serum Levels in Patients with Early Arthritis. International journal of molecular sciences 1 35806182
2026 Cancer-associated fibroblasts promote immune evasion in pancreatic cancer via miR-181b-5p/STING/LGALS1 pathway. Cancer letters 0 41713839
2026 GPX2+ tumor cells recruit LGALS1+ B cells via CCL26-CCR3 axis to promote immunosuppression and tumor progression in hepatocellular carcinoma. Frontiers in immunology 0 41939890
2026 LGALS1-CD276 Paracrine axis between tumor and endothelial cells promotes tumor angiogenesis and progression in bladder cancer. Cell death and differentiation 0 42230983
2025 Multi-omics analysis identified LGALS1 (Galectin-1) as a novel therapeutic target for clear cell renal cell carcinoma via targeting epithelial or endothelial cells. Discover oncology 0 41091247

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