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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LIF
LIF interleukin 6 family cytokine
Chromosome 22 · 22q12.2
NCBI Gene: 3976Ensembl: ENSG00000128342.5HGNC: HGNC:6596UniProt: P15018
244PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesiscell surface receptor signaling pathway via STATpositive regulation of receptor signaling pathway via STATpositive regulation of peptidyl-tyrosine phosphorylationalcohol drinkingfrozen shoulderlumbar disc herniationPalmar Fibromatosis
✦AI Summary

LIF (leukemia inhibitory factor) is a pleiotropic cytokine belonging to the interleukin-6 family that signals through a receptor complex consisting of LIF receptor β and gp130, activating JAK/STAT, MAPK, and PI3K pathways 1. Despite using common signaling mechanisms, LIF exhibits paradoxically opposite effects in different cell types, either stimulating or inhibiting cell proliferation, differentiation, and survival 1. LIF plays critical roles in maternal receptivity to blastocyst implantation, placental formation, nervous system development, and maintaining embryonic stem cell self-renewal and totipotency 1. In neural development, LIF regulates outer radial glial cell differentiation and promotes interneuron production in cortical cultures 2. LIF expression is widely distributed across human lung tissue, with the highest expression in fibroblasts, and is rapidly induced by inflammatory stimuli including IL-1β and anti-IgE 3. The cytokine's expression in monocytes is regulated by post-transcriptional mechanisms involving mRNA stabilization 4. In cancer, LIF promotes stemness and chemotherapy resistance through STAT3-SOX2 regulatory loops in head and neck squamous cell carcinoma 5 and pancreatic cancer 6. LIF knockout mice reveal that many of its cellular actions become apparent primarily during tissue damage or injury rather than normal development 1.

Sources cited
1
LIF is pleiotropic IL-6 family cytokine using LIF receptor β/gp130 complex, activates JAK/STAT/MAPK/PI3K pathways, has opposite effects in different cells, and is essential for blastocyst implantation and stem cell maintenance
PMID: 26187859
2
LIF signaling regulates outer radial glial cell differentiation and increases interneuron production in cortical development
PMID: 37673072
3
LIF is widely distributed in human lung tissue with highest expression in fibroblasts and is rapidly induced by IL-1β and anti-IgE
PMID: 10101017
4
LIF expression in monocytes is regulated by post-transcriptional mechanisms involving mRNA stabilization
PMID: 1940379
5
LIF promotes cancer stemness through STAT3-SOX2 regulatory loops in head and neck squamous cell carcinoma
PMID: 39206755
6
LIF promotes gemcitabine resistance in pancreatic cancer through STAT3 signaling
PMID: 35045883
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.24Weak
frozen shoulderOpen Targets
0.24Weak
lumbar disc herniationOpen Targets
0.23Weak
Palmar FibromatosisOpen Targets
0.23Weak
fibroblastic disorderOpen Targets
0.21Weak
glaucomaOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
cancerOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
open-angle glaucomaOpen Targets
0.11Weak
placenta praeviaOpen Targets
0.10Weak
gastric cancerOpen Targets
0.10Weak
uterine fibroidOpen Targets
0.10Weak
oral squamous cell carcinomaOpen Targets
0.10Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.10Suggestive
CachexiaOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
nasopharyngeal carcinomaOpen Targets
0.09Suggestive
infertilityOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OSMRProtein interaction100%LIFRProtein interaction100%POU5F1Protein interaction100%SOX2Protein interaction100%KLF4Protein interaction99%CNTFProtein interaction97%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
35%
Liver
20%
Heart
16%
Ovary
11%
Brain
3%
Gene Interaction Network
Click a node to explore
LIFOSMRLIFRPOU5F1SOX2KLF4CNTF
PROTEIN STRUCTURE
Preparing viewer…
PDB1PVH · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.62 [0.37–1.07]
RankingsWhere LIF stands among ~20K protein-coding genes
  • #1,594of 20,598
    Most Researched244 · top 10%
  • #10,871of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedLIF
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Leukemia inhibitory factor (LIF).
PMID: 26187859
Cytokine Growth Factor Rev · 2015
1.00
2
LIF signaling regulates outer radial glial to interneuron fate during human cortical development.
PMID: 37673072
Cell Stem Cell · 2023
0.90
3
circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis.
PMID: 35045883
Mol Cancer · 2022
0.80
4
Super-Enhancer Driven LIF/LIFR-STAT3-SOX2 Regulatory Feedback Loop Promotes Cancer Stemness in Head and Neck Squamous Cell Carcinoma.
PMID: 39206755
Adv Sci (Weinh) · 2024
0.70
5
LIF and multiple sclerosis: One protein with two healing properties.
PMID: 29448112
Mult Scler Relat Disord · 2018
0.68