scholarly journals Quantitative Glycoproteomics Analysis Identifies Novel FUT8 Targets and Signaling Networks Critical for Breast Cancer Cell Invasiveness

2021 ◽  
Author(s):  
Cheng-Fen Tu ◽  
Fu-An Li ◽  
Ling-Hui Li ◽  
Ruey-Bing Yang
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Ingenuity Pathway Analysis ◽  
Cancer Progression ◽  
Pathway Analysis ◽  
Signaling Networks ◽  
Comprehensive List ◽  
Core Fucosylation

Abstract BackgroundWe recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown.MethodWe performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, Ingenuity Pathway Analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC-MS/MS (liquid chromatography-tandem mass spectrometry) analysis.ResultsLoss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity Pathway Analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST is crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis.ConclusionsOur report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.

scholarly journals Integrated analysis of breast cancer cell lines reveals unique signaling pathways

2009 ◽  
Vol 10 (3) ◽  
pp. R31 ◽  
Author(s):  
Laura M Heiser ◽  
Nicholas J Wang ◽  
Carolyn L Talcott ◽  
Keith R Laderoute ◽  
Merrill Knapp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Integrated Analysis

scholarly journals Dietary Antioxidant Trans-Cinnamaldehyde Reduced Visfatin-Induced Breast Cancer Progression: In Vivo and In Vitro Study

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 625 ◽  
Author(s):  
Yi-Fen Chiang ◽  
Hsin-Yuan Chen ◽  
Ko-Chieh Huang ◽  
Po-Han Lin ◽  
Shih-Min Hsia
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Natural Compound ◽  
Cancer Cell Line ◽  
Nad Synthesis

Excessive growth of cancer cells is the main cause of cancer mortality. Therefore, discovering how to inhibit cancer growth is an important research topic. Recently, the newly discovered adipokine, known as nicotinamide phosphoribosyl transferase (NAMPT, visfatin), which has been associated with metabolic syndrome and obesity, has also been found to be a major cause of cancer proliferation. Therefore, inhibition of NAMPT and reduction of Nicotinamide adenine dinucleotide (NAD) synthesis is one strategy for cancer therapy. Cinnamaldehyde (CA), as an antioxidant and anticancer natural compound, may have the ability to inhibit visfatin. The breast cancer cell line and xenograft animal models were treated under different dosages of visfatin combined with CA and FK866 (a visfatin inhibitor) to test for cell toxicity, as well as inhibition of tumor-related proliferation of protein expression. In the breast cancer cell and the xenograft animal model, visfatin significantly increased proliferation-related protein expression, but combination with CA or FK866 significantly reduced visfatin-induced carcinogenic effects. For the first time, a natural compound inhibiting extracellular and intracellular NAMPT has been demonstrated. We hope that, in the future, this can be used as a potential anticancer compound and provide further directions for research.

scholarly journals The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion

2006 ◽  
Vol 13 (3) ◽  
pp. 895-903 ◽  
Author(s):  
J R Puddefoot ◽  
U K I Udeozo ◽  
S Barker ◽  
G P Vinson
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Angiotensin Ii ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Renin Angiotensin System ◽  
Adhesion And Invasion

As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelial cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin II (AII) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, AII (10−6 M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (P<0.001) and reduced invasion through collagen-, fibronectin- and laminin-coated membranes (P<0.05). This action was inhibited by co-treatment with the angiotensin type 1 receptor (AT1R) antagonist losartan (10−5 M). The addition of the AT2R inhibitor PD123319 (10−5 M) to AII-treated cells had no significant effect. Semi-quantitative reverse transcriptase-PCR and western blotting revealed that cells treated with AII (10−6 M) expressed lower levels of both integrin α3 and β1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that AII reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular α3 and β1.

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