R-Spondin 2 Promoted Proliferation, Invasion and Migration of Triple Negative Breast Cancer Cells Through Activating Wnt/β-Catenin Signaling Pathway After Axin2 Inhibition

2020 ◽  
Vol 10 (1) ◽  
pp. 26-36
Author(s):  
XiaoHu Sun ◽  
Yue Yu ◽  
Jie Ge ◽  
Xin Wang ◽  
XuChen Cao

Protein R-spondin 2, which is known as roof plate-specific spondin 2, is an extracellular matrix secreted protein that participates in a wide range of biological processes. However, the expression of R-spondin 2 in triple negative breast cancer (TNBC) and its specific mechanism have not been reported. In this study, RT-qPCR and western blot were used to detect the expression of R-spondin 2 and Axin2 in cells. Cell transfection techniques were used to overexpress Axin2 and interfere with the expression of R-spondin 2. CCk-8 and clone formation assay were used to detect cell viability. Wound healing and Traswell techniques were used to test the rate of invasion and migration of TNBC cells. Western blot was used to detect the expression of related proteins. The results showed that the expression of R-spondin 2 in TNBC cell lines was significantly increased compared with normal breast cancer cells. After interfering with the expression of R-spondin 2 in TNBC cell lines, the rate of cell viability, invasion and migration were decreased. It was also found that the expressions of Axin2 and β-catenin and Cyclin-D1, which are wnt/β-catenin pathway related proteins, were significantly decreased. Subsequently, the overexpression of Axin2 can inhibit the proliferation, invasion and migration that were ever promoted by R-spondin 2 of TNBC cells. Moreover, the overexpression of Axin2 inhibited the activation of wnt/β-catenin signaling pathway, which was also activated by R-spondin 2 in TNBC cells. In a word, R-spondin 2 promoted proliferation, invasion and migration of triple negative breast cancer cells through activating wnt/β-catenin signaling pathway after Axin2 inhibition.

2013 ◽  
Vol 220 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Hongzhong Li ◽  
Bing Yang ◽  
Jing Huang ◽  
Tingxiu Xiang ◽  
Xuedong Yin ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Qianxue Wu ◽  
Xin Tang ◽  
Wenming Zhu ◽  
Qing Li ◽  
Xiang Zhang ◽  
...  

BackgroundPatients with triple-negative breast cancer (TNBC) have poor overall survival. The present study aimed to investigate the potential prognostics of TNBC by analyzing breast cancer proteomic and transcriptomic datasets.MethodsCandidate proteins selected from CPTAC (the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium) were validated using datasets from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Kaplan-Meier analysis and ROC (receiver operating characteristic) curve analysis were performed to explore the prognosis of candidate genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed on the suspected candidate genes. Single-cell RNA-seq (scRNA-seq) data from GSE118389 were used to analyze the cell clusters in which OBFC2A (Oligosaccharide-Binding Fold-Containing Protein 2A) was mainly distributed. TIMER (Tumor Immune Estimation Resource) was used to verify the correlation between OBFC2A expression and immune infiltration. Clone formation assays and wound healing assays were used to detect the role of OBFC2A expression on the proliferation, invasion, and migration of breast cancer cells. Flow cytometry was used to analyze the effects of silencing OBFC2A on breast cancer cell cycle and apoptosis.ResultsSix candidate proteins were found to be differentially expressed in non-TNBC and TNBC groups from CPTAC. However, only OBFC2A was identified as an independently poor prognostic gene marker in METABRIC (HR=3.658, 1.881-7.114). And OBFC2A was associated with immune functions in breast cancer. Biological functional experiments showed that OBFC2A might promote the proliferation and migration of breast cancer cells. The inhibition of OBFC2A expression blocked the cell cycle in G1 phase and inhibited the transformation from G1 phase to S phase. Finally, downregulation of OBFC2A also increased the total apoptosis rate of cells.ConclusionOn this basis, OBFC2A may be a potential prognostic biomarker for TNBC.


PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167445 ◽  
Author(s):  
Miriam Fernandez-Gallardo ◽  
Ricardo González-Ramírez ◽  
Alejandro Sandoval ◽  
Ricardo Felix ◽  
Eduardo Monjaraz

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