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:C0027627 (
metastases
)
103,950
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Purpose:
The expression of FERM-domain-containing protein-1 (
FRMPD1
)/FERM and PDZ domain-containing protein-2 (FRMD2) in malignant tumors, including lung cancer, and its underlying molecular mechanism have not been reported yet.
Materials and methods:
Immunohistochemistry was performed to analyze the expression of
FRMPD1
in lung cancer tissues, and statistical analysis was applied to analyze the relationship between
FRMPD1
expression and clinicopathological factors. The biological effects of
FRMPD1
on lung cancer cell proliferation and invasion were determined by functional experiments both in vivo and in vitro. Immunoblotting, RT-qPCR, dual-luciferase assay, and immunofluorescence were performed to demonstrate whether
FRMPD1
stimulates Hippo signaling. Co-immunoprecipitation assays were used to clarify the underlying role of
FRMPD1
in Hippo pathway activation via interaction with WW and C2 domain containing protein-3 (WWC3).
Results:
We found that
FRMPD1
expression in lung cancer specimens was lower than that in normal bronchial epithelium and normal submucosal glands.
FRMPD1
expression had a negative correlation with age, Tumor-Node-
Metastasis
(TNM) stage, lymph node metastasis, as well as poor prognosis. Moreover, ectopic expression of
FRMPD1
significantly inhibited the proliferation and invasion of lung cancer cells, and inhibition of
FRMPD1
expression led to opposite effects. Mechanistically, we found that
FRMPD1
interacted with the C-terminal PDZ binding motif of WWC3 via its PSD95/DLG/ZO1 (PDZ) domain and promoted the phosphorylation of large tumor suppressor-1 (LATS1), thus inhibiting the nuclear translocation of yes-associated protein (YAP).
Conclusion:
FRMPD1
could activate the Hippo pathway and ultimately inhibit the malignant behavior of lung cancer cells through its interaction with WWC3. This work will provide an important experimental basis for the discovery of novel biomarkers of lung cancer and the development of targeted drugs.
...
PMID:FRMPD1 activates the Hippo pathway via interaction with WWC3 to suppress the proliferation and invasiveness of lung cancer cells. 3111 75
