| 2004 |
GW112 (OLFM4) physically associates with GRIM-19, and this interaction attenuates GRIM-19-mediated retinoic acid/IFN-β-induced cellular apoptosis and apoptosis-related gene expression; forced overexpression of GW112 in murine prostate tumor cells led to more rapid tumor formation in a syngeneic host. |
Co-immunoprecipitation (binding to GRIM-19), functional apoptosis assays, syngeneic tumor transplantation |
Cancer Research |
Medium |
15059901
|
| 2004 |
pDP4 (OLFM4) expression in myeloid cells is strictly dependent on the transcription factor PU.1, which binds to a functional site within the pDP4 promoter; the protein is a secreted 57-kDa glycoprotein predominantly expressed in mature neutrophils in bone marrow but markedly downregulated in peripheral blood and peritoneal neutrophils. |
PU.1-deficient mouse model, promoter-reporter assays, Western blot, subcellular fractionation/immunolocalization |
Blood |
High |
14962908
|
| 2008 |
G-CSF-induced OLFM4 expression in myeloid precursor cells is regulated by NF-κB binding to the OLFM4 proximal promoter; this induction is mediated through the PI3K-driven ROS→ERK1/2 MAPK pathway, and mutation of the NF-κB binding site in the promoter abolished transcription factor binding and OLFM4 expression. |
Promoter deletion/mutation reporter assays, EMSA, ChIP, pharmacological inhibitors (PI3K, ERK, ROS scavenger NAC), G-CSF stimulation of human CD34+ cells |
British Journal of Haematology |
High |
18764868
|
| 2010 |
NF-κB directly regulates GW112 (OLFM4) gene transcription by binding to a site between -442 and -430 of the GW112 promoter; knockdown or overexpression of GW112 in gastric cancer cells demonstrates it confers an antiapoptotic property against cytotoxic agent-induced apoptosis. |
Serial promoter deletion constructs, EMSA, ChIP, overexpression/siRNA knockdown in gastric cancer cell lines, apoptosis assays |
Molecular Carcinogenesis |
High |
19908244
|
| 2012 |
OLFM4 knockdown in gastric cancer cells (SGC-7901, MKN45) by RNA interference significantly inhibits tumorigenicity in vitro and in vivo by inducing G1 cell cycle arrest, and sensitizes cells to H2O2- or TNF-α-induced apoptosis through a caspase-3-dependent mechanism (reversed by Z-VAD-fmk). |
siRNA knockdown, cell proliferation/anchorage-independent growth assays, flow cytometry cell cycle analysis, caspase-3 activity assay, Z-VAD-fmk rescue, xenograft in vivo tumorigenicity |
Journal of Biomedical Science |
Medium |
22471589
|
| 2013 |
OLFM4 is a neutrophil granule protein localized to specific granules; OLFM4+ and OLFM4− neutrophil subsets are recruited equally to inflammatory sites in vivo; OLFM4 is released extracellularly through NET formation (not conventional degranulation), where it is detected in only a subset of NETs. |
Immunofluorescence localization to specific granules, in vivo transmigration models (acute experimental inflammation and pathological joint inflammation), NET formation assays, degranulation assays |
PloS One |
Medium |
23922742
|
| 2013 |
Olfm4 deletion enhances intracellular killing and in vivo clearance of Staphylococcus aureus and improves resistance to S. aureus sepsis in CGD mice; the mechanism involves increased activity of cathepsin C and its downstream proteases (neutrophil elastase and cathepsin G) and elevated inflammatory cytokines; Olfm4 deletion did not enhance defense against Aspergillus fumigatus. |
Olfm4-knockout mouse model, CGD double-knockout model, intracellular bacterial killing assays, in vivo challenge/clearance, cathepsin C/elastase/cathepsin G activity assays, cytokine measurement |
Journal of Clinical Investigation |
High |
23908114
|
| 2016 |
OLFM4 knockdown in gastric cancer cells promotes cell migration through activating the NF-κB/interleukin-8 axis; a negative correlation between OLFM4 and IL-8 expression was confirmed in early gastric cancer tumor samples. |
siRNA knockdown, cell migration assays, NF-κB/IL-8 pathway analysis, immunohistochemistry on patient samples |
Oncogenesis |
Medium |
27294866
|
| 2016 |
Estrogen receptor α (ERα) signaling induces OLFM4 expression in ovarian cancer cells in an ERα-dependent manner; miR-486-5p targets OLFM4 and decreases its mRNA expression; estrogen treatment reduces cellular miR-486-5p levels, thus relieving OLFM4 suppression; OLFM4 knockdown enhances proliferation, migration, and invasion of ovarian cancer cells. |
E2 treatment with ERα-dependent reporter assays, miR-486-5p mimic transfection, qRT-PCR, siRNA knockdown, proliferation/migration/invasion assays |
Oncotarget |
Medium |
26871282
|
| 2019 |
OLFM4 inhibits GRIM-19 expression in hepatocellular carcinoma cells, leading to enhanced STAT3 activation, increased cell cycle progression, and reduced apoptosis; double knockdown of GRIM-19 and OLFM4 restores STAT3 activation, confirming the OLFM4→GRIM-19→STAT3 axis; OLFM4 is also induced by LGR5-Wnt signaling in HCC cells. |
siRNA knockdown (single and double knockdown), STAT3 activation assays, cell cycle/apoptosis analysis, correlation analysis in 111 HCC patient specimens, in vitro LGR5 overexpression |
Hepatology Communications |
Medium |
31304451
|
| 2019 |
OLFM4 overexpression inhibits EMT, migration, and invasion in cervical cancer cells through interference with mTOR signaling; pharmacological activation of mTOR by phosphatidic acid largely reverses the suppressive effects of OLFM4 on migration and invasion. |
OLFM4 overexpression, mTOR pathway inhibition/activation with phosphatidic acid, migration/invasion assays, Western blot for EMT markers |
Oncology Research |
Low |
30764901
|
| 2019 |
OLFM4 expression in NSCLC cells is upregulated under hypoxia, and OLFM4 is a positive regulator of HIF-1α protein levels; depletion of OLFM4 under hypoxia reduces N-cadherin and vimentin while increasing E-cadherin (blocking EMT), and sensitizes cells to cisplatin. |
siRNA knockdown under hypoxic conditions, Western blot for HIF-1α and EMT markers, invasion assays, cisplatin sensitivity assays |
Journal of Cellular Physiology |
Low |
30680718
|
| 2020 |
In juvenile septic mice, OLFM4 is expressed in the kidney (localized to the loop of Henle); OLFM4-null pups show significantly increased survival, reduced renal cell apoptosis, and reduced plasma creatinine after sepsis induction; bone marrow transplant experiments indicate that increased kidney OLFM4 reflects local renal production rather than filtration from plasma. |
OLFM4-null mouse model, cecal ligation/puncture sepsis model, immunohistochemistry, creatinine measurement, apoptosis assay, bone marrow transplantation |
American Journal of Physiology - Renal Physiology |
Medium |
32068457
|
| 2021 |
Notch and TNF-α signaling synergistically upregulate OLFM4 transcription in intestinal epithelial cells (confirmed by luciferase reporter assay); this synergy promotes cytoplasmic accumulation of OLFM4 protein, which has antiapoptotic properties; patient-derived tissues and organoids confirmed cytoplasmic OLFM4 accumulation in response to NF-κB and Notch activation. |
Luciferase reporter assay, TNF-α and Notch pathway stimulation, immunofluorescence/immunohistochemistry, patient-derived organoids |
Biochemistry and Biophysics Reports |
Medium |
33490652
|
| 2021 |
OLFM4 in PMN-MDSCs mediates NF-κB/PTGS2 pathway activation through binding to LGALS3 (galectin-3, expressed on PMN-MDSCs); mice lacking OLFM4 in myeloid cells show poor PMN-MDSC recruitment, impaired intestinal homeostasis, and delayed colitis-to-colorectal cancer development, with increased response to anti-PD1 therapy. |
Myeloid-specific Olfm4-knockout mice, co-immunoprecipitation/binding assay (OLFM4-LGALS3 interaction), PMN-MDSC quantification, NF-κB/PTGS2 pathway analysis, tumor progression models |
Oncogene |
Medium |
35487976
|
| 2021 |
OLFM4 knockdown in rheumatoid arthritis fibroblast-like synoviocytes (FLS) under TNF-α stimulation inhibits FLS proliferation and decreases expression of CXCL9, CXCL11, and MMP-1, indicating OLFM4 promotes inflammatory signaling in FLS. |
siRNA knockdown in primary FLS under cytokine stimulation, proliferation assays, gene expression analysis |
Journal of Proteome Research |
Low |
34496567
|
| 2021 |
OLFM4-RET fusion protein induces cellular transformation in HEK293 cells and blocks RET-inhibition of colony growth; expression of OLFM4-RET activates the RAS-RAF-MAPK and STAT3 signaling pathways; targeted expression in mouse small intestine leads to hyperplasia, adenoma, or adenocarcinoma. |
Cellular transformation assay, colony growth assay, pathway activation (Western blot), transgenic mouse model |
Oncogene |
Medium |
34675408
|
| 2021 |
OLFM4 depletion in gallbladder cancer cells reduces ARL6IP1 expression and sensitizes cells to cisplatin both in vitro and in vivo; the mechanism involves CDDP-induced increase in Bax and Bad expression and caspase-3 cascade activation in OLFM4-depleted cells via ARL6IP1. |
siRNA knockdown, in vitro cisplatin resistance assays, in vivo xenograft, Western blot for apoptosis markers (Bax, Bad, caspase-3) |
Translational Oncology |
Medium |
34974280
|
| 2021 |
OLFM4 regulates lung epithelial cell pro-inflammatory responses in sepsis-related ARDS by modulating the LDHA phosphorylation/ROS/HIF-1α/NF-κB axis; OLFM4 overexpression and recombinant OLFM4 treatment suppressed LPS-induced NF-κB activation in lung epithelial cells by reducing ROS production and HIF-1α expression. |
OLFM4 overexpression, recombinant OLFM4 treatment, LPS stimulation, ROS measurement, Western blot for pLDHA/HIF-1α/NF-κB, CLP sepsis mouse model, immunofluorescence co-localization |
Journal of Inflammation Research |
Medium |
34955649
|
| 2024 |
OLFM4 is a negatively charged secreted neutrophil granule protein that inhibits neutrophil cationic protein (NCP) oligomerization through charge-based interference; this inhibition blocks neutrophil-mediated bacterial killing and TLR9 activation in plasmacytoid dendritic cells and neutrophils via DNA complex formation; OLFM4 inhibition enhances neutrophil-dependent bacterial killing, DNA complex formation, and accelerates skin wound closure. |
Structural/biophysical analysis of charge properties, OLFM4 addition/inhibition assays for NCP oligomerization, bacterial killing assays, TLR9 activation assays in pDCs and neutrophils, wound closure assays |
Cell Reports |
High |
39396234
|
| 2024 |
OLFM4 promotes ILC3-mediated intestinal inflammation by acting as a positive regulator of IL-22+ILC3; OLFM4 deficiency reduces IL-22 production by ILC3 through ASK1-p38 MAPK signaling-dependent downregulation of RORγt protein; the OLFM4-metadherin (MTDH) complex upregulates p38/RORγt signaling necessary for IL-22+ILC3 activation. |
OLFM4-knockout mice (full and RORγt-specific conditional), co-immunoprecipitation (OLFM4-MTDH complex), p38 MAPK/RORγt pathway analysis, IL-22 production assays, bacterial infection challenge |
Communications Biology |
Medium |
39075283
|
| 2024 |
EBV infection activates the cGAS-STING pathway and increases OLFM4 expression; OLFM4 is secreted via large microvesicles (MVs) and binds the extracellular cadherin domain of FAT1, impairing FAT1's intracellular interaction with MST1 and leading to YAP activation in recipient cells. |
EV/MV proteomics, cGAS-STING pathway inhibition/activation, co-immunoprecipitation (OLFM4-FAT1 extracellular domain; FAT1-MST1 intracellular interaction), YAP reporter assays |
Nature Communications |
High |
39627192
|
| 2024 |
OLFM4 promotes intestinal metaplasia progression by binding MYH9 (Myosin heavy chain 9), which together accelerates the ubiquitination of GSK3β, resulting in increased β-catenin levels through the Wnt signaling pathway and promoting cell proliferation and invasion. |
Co-immunoprecipitation (OLFM4-MYH9 interaction), GSK3β ubiquitination assay, β-catenin/Wnt pathway analysis, PLGC cell models, animal models, organoids |
Molecular Cancer |
Medium |
38849840
|
| 2024 |
Galectin-3 (Gal-3) stimulates OLFM4-mediated secretion of growth-promoting factors (GPFs) by placental PMN-MDSCs; GPF regulation via OLFM4 in placental PMN-MDSCs is mediated through HIF-1α; myeloid-specific Olfm4 knockout in female mice causes FGR during pregnancy with decreased placental PMN-MDSC populations and offspring intestinal inflammation. |
Myeloid-specific Olfm4-knockout mice, galectin-3 stimulation assays, HIF-1α pathway analysis, single-cell transcriptomics of placental PMN-MDSCs, GPF secretion assays |
International Immunopharmacology |
Medium |
38613883
|
| 2025 |
BAT-secreted OLFM4 traps Noggin (an endogenous BMP inhibitor), thereby liberating BMP7-BMPR1B signaling to promote Schwann cell differentiation; loss of Olfm4 in BAT reduces BMP7 signaling in mature Schwann cells, triggering MEK/ERK-dependent dedifferentiation, which impairs both sensory and sympathetic innervation of BAT and reduces thermogenesis. |
Olfm4-knockout mouse model, co-immunoprecipitation/binding assay (OLFM4-Noggin interaction), BMP7-BMPR1B pathway analysis, Schwann cell differentiation assays, MEK/ERK inhibition rescue, thermogenesis measurement |
Nature Communications |
High |
40467585
|
| 2026 |
RPSA deficiency induces overexpression of OLFM4 in neutrophils; elevated OLFM4 inhibits activation of the RhoA/ROCK1/pMLC2 signaling pathway, reduces MYH9 expression, and causes aberrant MYH9 translocation from the uropod to the cytosol in migrating neutrophils, disrupting cytoskeletal polarization and uropod extension to abrogate neutrophil migratory function. |
Myeloid-specific Rpsa-knockout mice, adoptive cell transfer, neutrophil depletion, OLFM4 overexpression, RhoA/ROCK1/pMLC2 pathway analysis, MYH9 localization by imaging, migration assays |
Nature Communications |
High |
42034613
|
| 2024 |
ARL6IP1 physically interacts with OLFM4 in breast cancer cells (confirmed by Co-IP); OLFM4 overexpression partially counteracts the suppression of glycolysis and pro-tumorigenic cell behavior caused by ARL6IP1 knockdown, placing OLFM4 downstream of ARL6IP1 in a glycolysis-regulatory axis. |
Co-immunoprecipitation (ARL6IP1-OLFM4 interaction), siRNA knockdown, OLFM4 overexpression rescue, Seahorse metabolic flux assay (ECAR, OCR), cell proliferation/invasion/migration assays |
Combinatorial Chemistry & High Throughput Screening |
Low |
40444622
|