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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

The novel TORC1/2 kinase inhibitor PQR620 has anti-tumor activity in lymphomas as a single agent and in combination with venetoclax

Tarantelli, Chiara ; Gaudio, Eugenio ; Hillmann, Petra ; Spriano, Filippo ; Sartori, Giulio ; Aresu, Luca ; Cascione, Luciano ; Rageot, Denise ; Kwee, Ivo ; Beaufils, Florent ; Zucca, Emanuele ; Stathis, Anastasios ; Wymann, Matthias P. ; Cmiljanovic, Vladimir ; Fabbro, Doriano ; Bertoni, Francesco

In: Cancers, 2019, vol. 11, no. 6, p. 775

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling cascade is an important therapeutic target for lymphomas. Rapamycin-derivates as allosteric mTOR complex 1 (TORC1) inhibitors have shown moderate preclinical and clinical anti-lymphoma activity. Here, we assessed the anti-tumor activity of PQR620, a novel brain penetrant dual TORC1/2 inhibitor, in 56...

Università della Svizzera italiana

Is there a role for dual PI3K/mTOR inhibitors for patients affected with lymphoma?

Tarantelli, Chiara ; Lupia, Antonio ; Stathis, Anastasios ; Bertoni, Francesco

In: International journal of molecular sciences, 2020, vol. 21, no. 3, p. 21 p

The activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti- cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical...

Université de Fribourg

Myosin 1b regulates nuclear AKT activation by preventing localization of PTEN in the nucleus

Yu, Yi ; Xiong, Yuyan ; Ladeiras, Diogo ; Yang, Zhihong ; Ming, Xiu-Fen

In: iScience, 2019, vol. 19, p. 39–53

Insulin-induced AKT activation is dependent on phosphoinositide 3-kinase and opposed by tumor suppressor phosphatase and tensin homolog (PTEN). Our previous study demonstrates that myosin 1b (MYO1B) mediates arginase-II-induced activation of mechanistic target of rapamycin complex 1 that is regulated by AKT. However, the role of MYO1B in AKT activation is unknown. Here we show that silencing...

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...

Università della Svizzera italiana

Epithelial-mesenchymal transition in cancer metastasis through the lymphatic syste

Karlsson, Mikael C. ; Gonzalez, Santiago F. ; Welin, Josefin ; Fuxe, Jonas

In: Molecular oncology, 2017, vol. 11, p. 781–791

It was already in the 18th century when the French surgeon LeDran first noted that breast cancer patients with spread of tumor cells to their axillary lymph nodes had a drastically worse prognosis than patients without spread (LeDran et al., ). Since then, metastatic spread of cancer cells to regional lymph nodes has been established as the most important prognostic factor in many types of...

Università della Svizzera italiana

Chemokine heterocomplexes and cancer : A novel chapter to be written in tumor immunity

D'Agostino, Gianluca ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2185

Infiltrating immune cells are a key component of the tumor microenvironment and play central roles in dictating tumor fate, either promoting anti-tumor immune responses, or sustaining tumor growth, angiogenesis and metastasis. A distinctive microenvironment is often associated to different tumor types, with substantial differences in prognosis. The production of a variety of chemotactic...

Università della Svizzera italiana

Regulatory control of DNA end resection by Sae2 phosphorylation

Cannavo, Elda ; Johnson, Dominic ; Andres, Sara N. ; Kissling, Vera M. ; Reinert, Julia K. ; Garcia, Valerie ; Erie, Dorothy A. ; Hess, Daniel ; Thomä, Nicolas H. ; Enchev, Radoslav I. ; Peter, Matthias ; Williams, R. Scott ; Neale, Matt J. ; Cejka, Petr

In: Nature communications, 2018, vol. 9, p. 4016

DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to...