
مجال التميز |
تميز دراسي وبحثي |
البحوث المنشورة |
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البحث (1): |
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عنوان البحث: |
Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential |
رابط إلى البحث: |
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تاريخ النشر: |
03/11/2015 |
موجز عن البحث: |
Breast cancer is the commonest form of cancer in women, but successful treatment is confounded by the heterogeneous nature of breast tumours: Effective treatments exist for hormone-sensitive tumours, but triple-negative breast cancer results in poor survival. An area of increasing interest is metabolic reprogramming, whereby drug-induced alterations in the metabolic landscape of a tumour slow tumour growth and/or increase sensitivity to existing therapeutics. Nuclear receptors are transcription factors central to the expression of metabolic and transport proteins, and thus represent potential targets for metabolic reprogramming. We show that activation of the nuclear receptor FXR, either by its endogenous ligand CDCA or the synthetic GW4064, leads to cell death in four breast cancer cell lines with distinct phenotypes: MCF-10A (normal), MCF-7 (receptor positive), MDA-MB-231 and MDA-MB-468 (triple negative). Furthermore, we show that the mechanism of cell death is predominantly through the intrinsic apoptotic pathway. Finally, we demonstrate that FXR agonists do not stimulate migration in breast cancer cell lines, an important potential adverse effect. Together, our data support the continued examination of FXR agonists as a novel class of therapeutics for the treatment of breast cancer. |
المؤتمرات العلمية: |
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المؤتمر (1): |
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عنوان المؤتمر: |
8th Saudi Students Conference |
تاريخ الإنعقاد: |
31/01-01/02/2015 |
مكان الإنعقاد: |
London, UK |
طبيعة المشاركة: |
Poster presentation |
عنوان المشاركة: |
Farnesoid X Receptor role on modulation of Matrix Metalloproteinases -2 and -9 in Metastatic Breast Cancer |
ملخص المشاركة: |
Advanced breast carcinoma is a main cause of mortality affecting women. It is associated with poor prognosis; therefore, understanding the molecular mechanisms of invasive malignancies is critical in order to discover new therapies. The aim of the current study was to investigate whether Farnesoid X receptor (FXR); a nuclear receptor which is highly expressed in Breast carcinoma is a novel regulator of matrix metalloprotease-2 and -9 (MMP-2 and-9) that play main role in breast cancer metastasis, and their endogenous inhibitors, Tissue inhibitors of metalloproteases (TIMPs). TIMP-2 and-1 inhibit MMP-2 and-9 respectively. Hence, FXR may represent a novel therapeutic target. Two FXR agonists were used to measure their effects on breast cancer cells MDA-MB-231, MDA-MB-468 (triple negative), MCF-7 (Estrogen receptor positive) and normal cells MCF10A: CDCA is an endogenous, while GW4064 is a synthetic ligand. Cell viability, protein and mRNA levels of matrix metalloprotease -2 and -9 and TIMP-2 and-1, and cell migration were assessed using both molecular and |
المؤتمر (2): |
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عنوان المؤتمر: |
7th Saudi Students Conference |
تاريخ الإنعقاد: |
1-2/02/2014 |
مكان الإنعقاد: |
Edinburgh, UK |
طبيعة المشاركة: |
Poster presentation |
عنوان المشاركة: |
Role of Farnesoid X Receptor in Regulation of Metastatic Breast Cancer |
ملخص المشاركة: |
Breast cancer is a primary cause of mortality in women and it is correlated to poor prognosis. Therefore, |
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المؤتمر (3): |
6th Saudi Students Conference |
عنوان المؤتمر: |
11-14 /10 /2012 |
تاريخ الإنعقاد: |
London, UK |
مكان الإنعقاد: |
Poster presentation |
طبيعة المشاركة: |
FXR Regulates Matrix Metalloproteinases in Breast Cancer |
عنوان المشاركة: |
Metastasis is associated with poor prognosis in breast cancer. Thus it is crucial to understand the molecular mechanisms of tumour cell invasion and metastasis in So the aim of this project was to investigate whether FXR is a novel regulator of MMP-2 and -9 in breast cancer cells. In conclusion, FXR activation by GW4064 increases secreted MMP-2 and -9 activity in breast cancer cells but this effect is not via transcriptional regulation of the MMPs or their inhibitory factors TIMP-1 or -2. |
المؤتمر (4): |
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عنوان المؤتمر: |
International Society for the Study of Xenobiotics (ISSX) |
تاريخ الإنعقاد: |
17/06/2012 |
مكان الإنعقاد: |
Noordwijjk, Netherlands |
طبيعة المشاركة: |
Poster presentation |
عنوان المشاركة: |
Regulation Of Matrix Metalloproteinases By FXR In Metastatic Breast Cancer |
ملخص المشاركة: |
Metastasis is associated with poor prognosis in breast cancer. Thus it is crucial to understand the molecular mechanisms of tumour cell invasion and metastasis in order to identify therapeutic targets. Metastasis requires degradation of the extracellular matrix (ECM), permitting cancer cells to invade and spread to distant sites. Matrix metalloproteinases (MMPs) are essential for degrading the proteins of the ECM. In particular, MMP-2 and -9 expression correlate with poor breast cancer prognosis. MMP activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 |
المؤتمر (5): |
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عنوان المؤتمر: |
5th Saudi Students Conference |
تاريخ الإنعقاد: |
23-26/06/2011 |
مكان الإنعقاد: |
Coventry, UK |
طبيعة المشاركة: |
Poster presentation |
عنوان المشاركة: |
The Role of Farnesoid X Receptor in Matrix Metalloproteinase Regulation in Breast Cancer |
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Breast cancer is a leading cause of female death in the UK. Therefore, developing new drugs is crucial. The nuclear receptor FXR is a potential novel therapeutic target. FXR is activated by bile acids, is expressed and is pro-apoptotic in breast cancers. Matrix |
المرفقات
- https://uksacb.org/wp-content/uploads/2015/11/ISSX-conference-.pdf
- https://uksacb.org/wp-content/uploads/2015/11/Saudi-conference-2012.pdf
- https://uksacb.org/wp-content/uploads/2015/11/Saudi-conference-2014.pdf
- https://uksacb.org/wp-content/uploads/2015/11/Saudi-conference2011.pdf
- https://uksacb.org/wp-content/uploads/2015/11/SIC-2015.pdf
- https://uksacb.org/wp-content/uploads/2015/11/ISSX-conference-.pdf
- https://uksacb.org/wp-content/uploads/2015/11/Saudi-conference-2012.pdf
- https://uksacb.org/wp-content/uploads/2015/11/Saudi-conference-2014.pdf
- https://uksacb.org/wp-content/uploads/2015/11/Saudi-conference2011.pdf
- https://uksacb.org/wp-content/uploads/2015/11/SIC-2015.pdf