scholarly journals O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR in breast cancer

2019 ◽  
Author(s):  
Virginia Tajadura-Ortega ◽  
Gennaro Gambardella ◽  
Alexandra Skinner ◽  
Katrine Ter-Borch Gram Schjoldager ◽  
Richard Beatson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Galectin 3 ◽  
Short Core ◽  
Regulate Gene

ABSTRACTAberrant mucin type O-linked glycosylation is a common occurrence in cancer. This type of O-linked glycosylation is not limited to mucins but can occur on many cell surface glycoproteins where only a small number of sites may be present. Upon EGF ligation, EGFR induces a signaling cascade but can also translocate to the nucleus where it can directly regulate gene transcription. Here we show that upon EGF binding, human breast cancer cells carrying different O-linked glycans respond by transcribing different gene expression signatures. This is not a result of changes in signal transduction but due to the differential nuclear translocation of EGFR in the two glyco-phenotypes. This is regulated by the formation of an EGFR/galectin-3/MUC1/β-catenin complex at the cell surface that is present in cells carrying short core-1-based O-glycans characteristic of tumour cells but absent in core-2-carrying cells.

scholarly journals ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Fabiana Sélos Guerra ◽  
Ramon Guerra de Oliveira ◽  
Carlos Alberto Manssour Fraga ◽  
Claudia dos Santos Mermelstein ◽  
Patricia Dias Fernandes
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Beta Catenin ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Rock Inhibition

scholarly journals MEK inhibition leads to lysosome-mediated Na+/I− symporter protein degradation in human breast cancer cells

2013 ◽  
Vol 20 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Zhaoxia Zhang ◽  
Sasha Beyer ◽  
Sissy M Jhiang
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Tumors ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Iodide Uptake ◽  
Mek Inhibition ◽  
Protein Levels

The Na+/I−symporter (NIS (SLC5A5)) is a transmembrane glycoprotein that mediates active iodide uptake into thyroid follicular cells. NIS-mediated iodide uptake in thyroid cells is the basis for targeted radionuclide imaging and treatment of differentiated thyroid carcinomas and their metastases. Furthermore, NIS is expressed in many human breast tumors but not in normal non-lactating breast tissue, suggesting that NIS-mediated radionuclide uptake may also allow the imaging and targeted therapy of breast cancer. However, functional cell surface NIS expression is often low in breast cancer, making it important to uncover signaling pathways that modulate NIS expression at multiple levels, from gene transcription to posttranslational processing and cell surface trafficking. In this study, we investigated NIS regulation in breast cancer by MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) signaling, an important cell signaling pathway involved in oncogenic transformation. We found that MEK inhibition decreased NIS protein levels in all-trans retinoic acid/hydrocortisone-treated MCF-7 cells as well as human breast cancer cells expressing exogenous NIS. The decrease in NIS protein levels by MEK inhibition was not accompanied by a decrease inNISmRNA or a decrease inNISmRNA export from the nucleus to the cytoplasm. NIS protein degradation upon MEK inhibition was prevented by lysosome inhibitors but not by proteasome inhibitors. Interestingly, NIS protein level was correlated with MEK/ERK activation in human breast tumors from a tissue microarray. Taken together, MEK activation appears to play an important role in maintaining NIS protein stability in human breast cancers.

Hypoxia and estrogen co-operate to regulate gene expression in T-47D human breast cancer cells

2007 ◽  
Vol 104 (3-5) ◽  
pp. 169-179 ◽  
Author(s):  
Ramzi Seifeddine ◽  
Anne Dreiem ◽  
Céline Tomkiewicz ◽  
Marie-Claude Fulchignoni-Lataud ◽  
Isabel Brito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Regulate Gene Expression ◽  
Regulate Gene

scholarly journals A galectin-3 sequence polymorphism confers TRAIL sensitivity to human breast cancer cells

Cancer ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 4375-4380 ◽  
Author(s):  
Nachman Mazurek ◽  
James C. Byrd ◽  
Yunjie Sun ◽  
Suguru Ueno ◽  
Robert S. Bresalier
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Sequence Polymorphism ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Galectin 3 ◽  
Trail Sensitivity

scholarly journals Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2997 ◽  
Author(s):  
Kyu-Shik Lee ◽  
Min-Gu Lee ◽  
Yun-Suk Kwon ◽  
Kyung-Soo Nam
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Dependent Manner ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Concentration Dependent Manner

Several reports have described the anti-cancer activity of arctigenin, a lignan extracted from Arctium lappa L. Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial BAX levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX.

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