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Université de Fribourg

β-Arrestin1 and β-Arrestin2 are required to support the activity of the CXCL12/HMGB1 heterocomplex on CXCR4

D’Agostino, Gianluca ; Artinger, Marc ; Locati, Massimo ; Perez, Laurent ; Legler, Daniel F. ; Bianchi, Marco E. ; Rüegg, Curzio ; Thelen, Marcus ; Marchese, Adriano ; Rocchi, Marco B. L. ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in Immunology, 2020, vol. 11, p. -

The chemokine receptor CXCR4 plays a fundamental role in homeostasis and pathology by orchestrating recruitment and positioning of immune cells, under the guidance of a CXCL12 gradient. The ability of chemokines to form heterocomplexes, enhancing their function, represents an additional level of regulation on their cognate receptors. In particular, the multi-faceted activity of the...

Université de Fribourg

Targeting the extra-cellular matrix—tumor cell crosstalk for anti-cancer therapy: emerging alternatives to integrin inhibitors

Lorusso, Girieca ; Rüegg, Curzio ; Kuonen, François

In: Frontiers in Oncology, 2020, vol. 10, p. -

The extracellular matrix (ECM) is a complex network composed of a multitude of different macromolecules. ECM components typically provide a supportive structure to the tissue and engender positional information and crosstalk with neighboring cells in a dynamic reciprocal manner, thereby regulating tissue development and homeostasis. During tumor progression, tumor cells commonly modify and...

Université de Fribourg

CD47 promotes age-associated deterioration in angiogenesis, blood flow and glucose homeostasis

Ghimire, Kedar ; Li, Yao ; Chiba, Takuto ; Julovi, Sohel M. ; Li, Jennifer ; Ross, Mark A. ; Straub, Adam C. ; O’Connell, Philip J. ; Rüegg, Curzio ; Pagano, Patrick J. ; Isenberg, Jeffrey S. ; Rogers, Natasha M.

In: Cells, 2020, vol. 9, no. 7, p. 1695

The aged population is currently at its highest level in human history and is expected to increase further in the coming years. In humans, aging is accompanied by impaired angiogenesis, diminished blood flow and altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of aging can be a suitable target for therapeutic intervention. Here we identify cell...

Université de Fribourg

Magi1, a new potential tumor suppressor gene in estrogen receptor positive breast cancer

Alday-Parejo, Begoña ; Richard, François ; Wörthmüller, Janine ; Rau, Tilman ; Galván, José A. ; Desmedt, Christine ; Santamaria-Martinez, Albert ; Rüegg, Curzio

In: Cancers, 2020, vol. 12, no. 1, p. 223

Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts...

Université de Fribourg

Detection of HER2+ breast cancer cells using bioinspired DNA-based signal amplification

Rafiee, Sarah D. ; Kocabey, Samet ; Mayer, Michael ; List, Jonathan ; Rüegg, Curzio

In: ChemMedChem, 2020, vol. 15, no. 8, p. 661-666

Circulating tumor cells (CTC) are promising biomarkers for metastatic cancer detection and monitoring progression. However, detection of CTCs remains challenging due to their low frequency and heterogeneity. Herein, we report a bioinspired approach to detect individual cancer cells, based on a signal amplification cascade using a programmable DNA hybridization chain reaction (HCR) circuit. We...

Université de Fribourg

Are integrins still practicable targets for anti-cancer therapy?

Alday-Parejo, Begoña ; Stupp, Roger ; Rüegg, Curzio

In: Cancers, 2019, vol. 11, no. 7, p. 978

Correlative clinical evidence and experimental observations indicate that integrin adhesion receptors, in particular those of the αV family, are relevant to cancer cell features, including proliferation, survival, migration, invasion, and metastasis. In addition, integrins promote events in the tumor microenvironment that are critical for tumor progression and metastasis, including tumor...

Université de Fribourg

Breast cancer stem cells with tumor- versus metastasis-initiating capacities are modulated by TGFBR1 inhibition

Fico, Flavia ; Bousquenaud, Mélanie ; Rüegg, Curzio ; Santamaria-Martínez, Albert

In: Stem Cell Reports, 2019, vol. 13, no. 1, p. 1–9

Cancer stem cells (CSCs) are defined by their ability to regenerate a tumor upon transplantation. However, it is not yet clear whether tumors contain a single CSC population or different subsets of cells with mixed capacities for initiating primary and secondary tumors. Using two different identification strategies, we studied the overlap between metastatic stem cells and tumor-initiating...

Université de Fribourg

MAGI1 mediates eNOS activation and NO production in endothelial cells in response to fluid shear stress

Ghimire, Kedar ; Zaric, Jelena ; Alday-Parejo, Begoña ; Seebach, Jochen ; Bousquenaud, Mélanie ; Stalin, Jimmy ; Bieler, Grégory ; Schnittler, Hans-Joachim ; Rüegg, Curzio

In: Cells, 2019, vol. 8, no. 5, p. 388

Fluid shear stress stimulates endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production through multiple kinases, including protein kinase A (PKA), AMP-activated protein kinase (AMPK), AKT and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an adaptor protein that...

Université de Fribourg

Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer

Lan, Qiang ; Peyvandi, Sanam ; Duffey, Nathalie ; Huang, Yu-Ting ; Barras, David ; Held, Werner ; Richard, François ; Delorenzi, Mauro ; Sotiriou, Christos ; Desmedt, Christine ; Lorusso, Girieca ; Rüegg, Curzio

In: Oncogene, 2019, vol. 38, no. 15, p. 2814–2829

Neoadjuvant and adjuvant chemotherapies provide survival benefits to breast cancer patients, in particular in estrogen receptor negative (ER−) cancers, by reducing rates of recurrences. It is assumed that the benefits of (neo)adjuvant chemotherapy are due to the killing of disseminated, residual cancer cells, however, there is no formal evidence for it. Here, we provide experimental...