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Università della Svizzera italiana

A novel prostate cell type-specific gene signature to interrogate prostate tumor differentiation status and monitor therapeutic response (running title: Phenotypic classification of prostate tumors)

Mapelli, Sarah N. ; Albino, Domenico ; Mello-Grand, Maurizia ; Shinde, Dheeraj ; Scimeca, Manuel ; Bonfiglio, Rita ; Bonanno, Elena ; Chiorino, Giovanna ; Garcia-Escudero, Ramon ; Catapano, Carlo V. ; Carbone, Giuseppina M.

In: Cancers, 2020, vol. 12, no. 1, p. 23 p

In this study, we extracted prostate cell-specific gene sets (metagenes) to define the epithelial differentiation status of prostate cancers and, using a deconvolution-based strategy, interrogated thousands of primary and metastatic tumors in public gene profiling datasets. We identified a subgroup of primary prostate tumors with low luminal epithelial enrichment (LumElow). LumElow tumors were...

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....

Università della Svizzera italiana

Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells

Genini, Davide ; Brambilla, Lara ; Laurini, Erik ; Merulla, Jessica ; Civenni, Gianluca ; Pandit, Shusil ; D'Antuono, Rocco ; Perez, Laurent ; Levy, David E. ; Pricl, Sabrina ; Carbone, Giuseppina M. ; Catapano, Carlo V.

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 25, p. E4924-E4933

In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The...