RGD Reference Report - Fibulin-4 is associated with prognosis of endometrial cancer patients and inhibits cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway. - Rat Genome Database

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Fibulin-4 is associated with prognosis of endometrial cancer patients and inhibits cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway.

Authors: Wang, Tiantian  Wang, Mei  Fang, Shuang  Wang, Qiang  Fang, Rui  Chen, Jie 
Citation: Wang T, etal., Oncotarget. 2017 Mar 21;8(12):18991-19012. doi: 10.18632/oncotarget.15086.
RGD ID: 42722012
Pubmed: PMID:28177909   (View Abstract at PubMed)
PMCID: PMC5386664   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.15086   (Journal Full-text)

Fibulin-4, an extracellular glycoprotein, which plays significant roles in elastic fiber assembly, is correlated to the progression of some cancers. However, the role of fibulin-4 in endometrial cancer cell invasion and metastasis remains unexplored. In our study, fibulin-4 expression was assessed by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in normal endometrial tissues and endometrial carcinoma tissues. Using single cell cloning, strongly, and weakly, invasive subclones were derived from KLE and Ishikawa endometrial carcinoma cell lines. RT-qPCR, western blotting, and immunocytochemistry (ICC) were used to assess mRNA and protein expressions of fibulin-4 in primary cultured endometrial cells, 4 types of endometrial cancer cell lines, and the different invasive subclones. Using lentivirus transfection, fibulin-4 shRNA and pLVX-fibulin-4 were constructed and used to infect the strongly and weakly invasive subclones. The effects of fibulin-4 on the biological characteristics of endometrial carcinoma cells were detected by cell functional assays in vitro and in vivo. Using Wnt signaling pathway inhibitor XAV-939 and activator LiCl, we detected the role of fibulin-4 in the Wnt/β-catenin pathway and the relationship with epithelial to mesenchymal transition (EMT). Fibulin-4 was decreased in endometrial carcinoma tissues, and loss of fibulin-4 expression was significantly related with poor differentiation, lymph node metastasis, and poor prognosis of endometrial carcinoma. Fibulin-4 significantly inhibited endometrial carcinoma cell proliferation, invasion, metastasis, and EMT through the Wnt/β-catenin pathway. Fibulin-4 has the ability to suppress endometrial cancer progression. These results can contribute to the development of a new potential therapeutic target for patients with endometrial carcinoma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial cancer amelioratesIMP 42722012human EFEMP2 knockdown cell line in a mouse modelRGD 
endometrial cancer exacerbatesIEP 42722012protein:decreased expression:endometrium (human)RGD 
endometrial cancer amelioratesISOEFEMP2 (Homo sapiens)42722012; 42722012human EFEMP2 knockdown cell line in a mouse modelRGD 
endometrial cancer exacerbatesISOEFEMP2 (Homo sapiens)42722012; 42722012protein:decreased expression:endometrium (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Efemp2  (EGF containing fibulin extracellular matrix protein 2)

Genes (Mus musculus)
Efemp2  (epidermal growth factor-containing fibulin-like extracellular matrix protein 2)

Genes (Homo sapiens)
EFEMP2  (EGF containing fibulin extracellular matrix protein 2)


Additional Information