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Università della Svizzera italiana

Retinoic acid sensitivity of triple-negative breast cancer cells characterized by constitutive activation of the NOTCH1 pathway : the role of RARβ

Paroni, Gabriela ; Zanetti, Adriana ; Barzago, Maria Monica ; Kurosaki, Mami ; Guarrera, Luca ; Fratelli, Maddalena ; Troiani, Martina ; Ubezio, Paolo ; Bolis, Marco ; Vallerga, Arianna ; Biancardi, Federica ; Terao, Mineko ; Garattini, Enrico

In: Cancers, 2020, vol. 12, no. 10, p. 23 p

Triple-negative breast cancer (TNBC) is a heterogeneous disease that lacks effective therapeutic options. In this study, we profile eighteen TNBC cell lines for their sensitivity to the anti-proliferative action of all-trans retinoic acid (ATRA). The only three cell lines (HCC-1599, MB- 157 and MDA-MB-157) endowed with ATRA-sensitivity are characterized by genetic aberrations of the NOTCH1-gene,...

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

Role of akt activation in PARP inhibitor resistance in cancer

Gallyas, Ferenc ; Sumegi, Balazs ; Szabo, Csaba

In: Cancers, 2020, vol. 12, no. 3, p. 532

Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mechanisms are not fully understood. Activity of the cytoprotective phosphatidylinositol-3 kinase...

Università della Svizzera italiana

Multi-targeting bioactive compounds extracted from essential oils as kinase inhibitors

Maruca, Annalisa ; Lanzillotta, Delia ; Rocca, Roberta ; Lupia, Antonio ; Costa, Giosuè ; Catalano, Raffaella ; Moraca, Federica ; Gaudio, Eugenio ; Ortuso, Francesco ; Artese, Anna ; Trapasso, Francesco ; Alcaro, Stefano

In: Molecules, 2020, vol. 25, no. 9, p. 14 p

Essential oils (EOs) are popular in aromatherapy, a branch of alternative medicine that claims their curative effects. Moreover, several studies reported EOs as potential anti- cancer agents by inducing apoptosis in different cancer cell models. In this study, we have considered EOs as a potential resource of new kinase inhibitors with a polypharmacological profile. On the other hand,...

Université de Fribourg

Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

Brenna, Andrea ; Olejniczak, Iwona ; Chavan, Rohit ; Ripperger, Jürgen A. ; Langmesser, Sonja ; Cameroni, Elisabetta ; Hu, Zehan ; De Virgilio, Claudio ; Dengjel, Jörn ; Albrecht, Urs

In: eLife, 2019, vol. 8, p. e50925

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5...

Université de Fribourg

Regulation of TRPM8 channel activity by Src-mediated tyrosine phosphorylation

Manolache, Alexandra ; Selescu, Tudor ; Maier, G. Larisa ; Mentel, Mihaela ; Ionescu, Aura Elena ; Neacsu, Cristian ; Babes, Alexandru ; Szedlacsek, Stefan Eugen

In: Journal of Cellular Physiology, 2019, p. -

The transient receptor potential melastatin type 8 (TRPM8) receptor channel is expressed in primary afferent neurons where it is the main transducer of innocuous cold temperatures and also in a variety of tumors, where it is involved in progression and metastasis. Modulation of this channel by intracellular signaling pathways has therefore important clinical implications. We investigated the...

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...

Università della Svizzera italiana

Hitting the right spot : mechanism of action of OPB‐31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3)

Brambilla, Lara ; Genini, Davide ; Laurini, Erik ; Merulla, Jessica ; Perez, Laurent ; Fermeglia, Maurizio ; Carbone, Giuseppina M. ; Pricl, Sabrina ; Catapano, Carlo V.

In: Molecular oncology, 2015, vol. 9, no. 6, p. 1194-1206

STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB‐31121, an anticancer compound currently in clinical trials, has been reported to affect...

Università della Svizzera italiana

Structural biology of STAT3 and its implications for anticancer therapies development

Sgrignani, Jacopo ; Garofalo, Maura ; Matkovic, Milos ; Merulla, Jessica ; Catapano, Carlo V. ; Cavalli, Andrea

In: International journal of molecular sciences, 2018, vol. 19, no. 6, p. 1591

Transcription factors are proteins able to bind DNA and induce the transcription of specific genes. Consequently, they play a pivotal role in multiple cellular pathways and are frequently over-expressed or dysregulated in cancer. Here, we will focus on a specific “signal transducer and activator of transcription” (STAT3) factor that is involved in several pathologies, including cancer....