Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1522282 (
EMT
)
2,868
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chronic inflammation has been linked to promotion of tumorigenesis and metastasis in lung. However, due to lack of a relevant animal model for characterization, the underlying mechanism remains elusive. Lung tumor suppressor gene Gprc5a-knockout (ko) mice are susceptible to lung inflammation, tumorigenesis and metastasis, which resembles the pathological features in human patients. Here, we showed that
PTGES
/PGE
2
signaling was highly associated with lung tumorigenesis and metastasis in Gprc5a-ko mice. Interestingly, Ptges-knockout in mouse lung tumor cells, although reduced their stemness and
EMT
-like features, still formed tumors and lung metastasis in immune-deficient nude mice, but not in immune-competent mice. This suggests that the major role of
PTGES
/PGE
2
signaling in tumorigenicity and lung metastasis is through immunosuppression. Mechanistically,
PTGES
/PGE
2
signaling intrinsically endows tumor cells resistant to T-cell cytotoxicity, and induces cytokines extrinsically for MDSC recruitment, which is crucial for suppression of T-cell immunity. Importantly, targeting PGE
2
signaling in Gprc5a-ko mice by
PTGES
inhibitor suppressed MDSC recruitment, restored T cells, and significantly repressed lung metastasis. Thus,
PTGES
/PGE
2
signaling links immunosuppression and metastasis in an inflammatory lung microenvironment of Gprc5a-ko mouse model.
...
PMID:PTGES/PGE
2
signaling links immunosuppression and lung metastasis in Gprc5a-knockout mouse model. 3206 Apr 21
