7 results on '"Pellarin, Ilenia"'
Search Results
2. CDK6 protects epithelial ovarian cancer from platinum‐induced death via FOXO3 regulation
- Author
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Dall'Acqua, Alessandra, Sonego, Maura, Pellizzari, Ilenia, Pellarin, Ilenia, Canzonieri, Vincenzo, D'Andrea, Sara, Benevol, Sara, Sorio, Roberto, Giorda, Giorgio, Califano, Daniela, Bagnoli, Marina, Militello, Loredana, Mezzanzanica, Delia, Chiappetta, Gennaro, Armenia, Joshua, Belletti, Barbara, Schiappacassi, Monica, and Baldassarre, Gustavo
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- 2017
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3. RNA splicing alteration in the response to platinum chemotherapy in ovarian cancer: A possible biomarker and therapeutic target.
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Pellarin, Ilenia, Belletti, Barbara, and Baldassarre, Gustavo
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RNA splicing ,CANCER chemotherapy ,OVARIAN cancer ,BIOMARKERS ,PLATINUM - Abstract
Since its discovery, alternative splicing has been recognized as a powerful way for a cell to amplify the genetic information and for a living organism to adapt, evolve, and survive. We now know that a very high number of genes are regulated by alternative splicing and that alterations of splicing have been observed in different types of human diseases, including cancer. Here, we review the accumulating knowledge that links the regulation of alternative splicing to the response to chemotherapy, focusing our attention on ovarian cancer and platinum‐based treatments. Moreover, we discuss how expanding information could be exploited to identify new possible biomarkers of platinum response, to better select patients, and/or to design new therapies able to overcome platinum resistance. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Identification and Characterization of a New Platinum-Induced TP53 Mutation in MDAH Ovarian Cancer Cells.
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Lorenzon, Ilaria, Pellarin, Ilenia, Pellizzari, Ilenia, D’Andrea, Sara, Belletti, Barbara, Sonego, Maura, Baldassarre, Gustavo, and Schiappacassi, Monica
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CANCER cells , *OVARIAN cancer , *OVARIAN epithelial cancer , *MULTINUCLEATED giant cells , *CELL cycle , *CELL lines - Abstract
Platinum-based chemotherapy is the therapy of choice for epithelial ovarian cancer (EOC). Acquired resistance to platinum (PT) is a frequent event that leads to disease progression and predicts poor prognosis. To understand possible mechanisms underlying acquired PT-resistance, we have recently generated and characterized three PT-resistant isogenic EOC cell lines. Here, we more deeply characterize several PT-resistant clones derived from MDAH-2774 cells. We show that, in these cells, the increased PT resistance was accompanied by the presence of a subpopulation of multinucleated giant cells. This phenotype was likely due to an altered progression through the M phase of the cell cycle and accompanied by the deregulated expression of genes involved in M phase progression known to be target of mutant TP53. Interestingly, we found that PT-resistant MDAH cells acquired in the TP53 gene a novel secondary mutation (i.e., S185G) that accompanied the R273H typical of MDAH cells. The double p53S185G/R273H mutant increases the resistance to PT in a TP53 null EOC cellular model. Overall, we show how the selective pressure of PT is able to induce additional mutation in an already mutant TP53 gene in EOC and how this event could contribute to the acquisition of novel cellular phenotypes. [ABSTRACT FROM AUTHOR]
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- 2020
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- View/download PDF
5. USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability.
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Sonego, Maura, Pellarin, Ilenia, Costa, Alice, Coan, Michela, D'Andrea, Sara, Dall'Acqua, Alessandra, Spizzo, Riccardo, Belletti, Barbara, Schiappacassi, Monica, Baldassarre, Gustavo, Vinciguerra, Gian Luca Rampioni, Vecchione, Andrea, Kraut, Alexandra, Couté, Yohann, Castillo-Tong, Dan Cacsire, Califano, Daniela, and Losito, Simona
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OVARIAN cancer , *CANCER chemotherapy , *CANCER patients , *METASTASIS , *UBIQUITIN - Abstract
The article talks about resistance to platinum-based chemotherapy being a common event in cancer patients, which is generally associated with tumor dissemination and metaatasis. Topics discussed include the article reporting the ubiquitin-specific protease 1 (USP1) mediating ovarian cancer cell resistance which promotes tumor dissemination.
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- 2019
- Full Text
- View/download PDF
6. CDK6 protects epithelial ovarian cancer from platinum‐induced death via FOXO3 regulation
- Author
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Delia Mezzanzanica, Monica Schiappacassi, Maura Sonego, Giorgio Giorda, Alessandra Dall'Acqua, Sara D'Andrea, Barbara Belletti, Ilenia Pellarin, Roberto Sorio, Daniela Califano, Gennaro Chiappetta, Loredana Militello, Ilenia Pellizzari, Sara Benevol, Joshua Armenia, Marina Bagnoli, Gustavo Baldassarre, Vincenzo Canzonieri, Dall'Acqua, Alessandra, Sonego, Maura, Pellizzari, Ilenia, Pellarin, Ilenia, Canzonieri, Vincenzo, D'Andrea, Sara, Benevol, Sara, Sorio, Roberto, Giorda, Giorgio, Califano, Daniela, Bagnoli, Marina, Militello, Loredana, Mezzanzanica, Delia, Chiappetta, Gennaro, Armenia, Joshua, Belletti, Barbara, Schiappacassi, Monica, and Baldassarre, Gustavo
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0301 basic medicine ,endocrine system diseases ,Pyridines ,Ataxia Telangiectasia Mutated Proteins ,Carcinoma, Ovarian Epithelial ,Piperazines ,Mice ,platinum sensitivity ,Neoplasms, Glandular and Epithelial ,Research Articles ,Cancer ,Ovarian Neoplasms ,Cell Death ,biology ,Forkhead Box Protein O3 ,ATR ,CDK6 ,FOXO3 ,ovarian cancer ,Primary tumor ,female genital diseases and pregnancy complications ,Molecular Medicine ,Female ,Research Article ,Programmed cell death ,DNA damage ,Primary Cell Culture ,Urogenital System ,Mice, Nude ,Antineoplastic Agents ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Gene silencing ,Pharmacology & Drug Discovery ,Protein Kinase Inhibitors ,Transcription factor ,Platinum ,Cyclin-Dependent Kinase 6 ,medicine.disease ,Survival Analysis ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Apoptosis ,Immunology ,biology.protein ,Cancer research ,Cyclin-dependent kinase 6 ,Ovarian cancer ,DNA Damage - Abstract
Epithelial ovarian cancer (EOC) is an infrequent but highly lethal disease, almost invariably treated with platinum‐based therapies. Improving the response to platinum represents a great challenge, since it could significantly impact on patient survival. Here, we report that silencing or pharmacological inhibition of CDK6 increases EOC cell sensitivity to platinum. We observed that, upon platinum treatment, CDK6 phosphorylated and stabilized the transcription factor FOXO3, eventually inducing ATR transcription. Blockage of this pathway resulted in EOC cell death, due to altered DNA damage response accompanied by increased apoptosis. These observations were recapitulated in EOC cell lines in vitro , in xenografts in vivo , and in primary tumor cells derived from platinum‐treated patients. Consistently, high CDK6 and FOXO3 expression levels in primary EOC predict poor patient survival. Our data suggest that CDK6 represents an actionable target that can be exploited to improve platinum efficacy in EOC patients. As CDK4/6 inhibitors are successfully used in cancer patients, our findings can be immediately transferred to the clinic to improve the outcome of EOC patients.
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- 2017
7. USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability
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Simona Losito, Yohann Couté, Barbara Belletti, Michela Coan, Dan Cacsire Castillo-Tong, Ilenia Pellarin, Daniela Califano, Alice Costa, Sara D'Andrea, Monica Schiappacassi, Riccardo Spizzo, Maura Sonego, Alessandra Dall'Acqua, Gian Luca Rampioni Vinciguerra, Andrea Vecchione, Gustavo Baldassarre, Alexandra Kraut, Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Sonego, Maura, Pellarin, Ilenia, Costa, Alice, Vinciguerra, Gian Luca Rampioni, Coan, Michela, Kraut, Alexandra, D'Andrea, Sara, Dall'Acqua, Alessandra, Castillo-Tong, Dan Cacsire, Califano, Daniela, Losito, Simona, Spizzo, Riccardo, Couté, Yohann, Vecchione, Andrea, Belletti, Barbara, Schiappacassi, Monica, and Baldassarre, Gustavo
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endocrine system diseases ,[SDV]Life Sciences [q-bio] ,Apoptosis ,Drug resistance ,Snail ,Ataxia Telangiectasia Mutated Proteins ,Metastasis ,Mice ,0302 clinical medicine ,RNA interference ,Coordination Complexes ,Phosphorylation ,RNA, Small Interfering ,Research Articles ,ComputingMilieux_MISCELLANEOUS ,Cancer ,Gene Editing ,Ovarian Neoplasms ,0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,SciAdv r-articles ,female genital diseases and pregnancy complications ,Ovarian Cancer ,3. Good health ,030220 oncology & carcinogenesis ,Female ,RNA Interference ,Ubiquitin-Specific Proteases ,Research Article ,endocrine system ,Mice, Nude ,03 medical and health sciences ,biology.animal ,Cell Line, Tumor ,parasitic diseases ,medicine ,Animals ,Humans ,030304 developmental biology ,Platinum ,fungi ,Ubiquitination ,medicine.disease ,Xenograft Model Antitumor Assays ,USP1 ,Cell culture ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,Snail Family Transcription Factors ,Ovarian cancer ,platrinum resistance - Abstract
Snail is a target of USP1 that links platinum response to metastasis in ovarian cancer., Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated with tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked to tumor spreading is not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance to platinum, by regulating the stability of Snail, which, in turn, promotes tumor dissemination. At the molecular level, we observed that upon platinum treatment, USP1 is phosphorylated by ATM and ATR and binds to Snail. Then, USP1 de-ubiquitinates and stabilizes Snail expression, conferring resistance to platinum, increased stem cell–like features, and metastatic ability. Consistently, knockout or pharmacological inhibition of USP1 increased platinum sensitivity and decreased metastatic dissemination in a Snail-dependent manner. Our findings identify Snail as a USP1 target and open the way to a novel strategy to overcome platinum resistance and more successfully treat patients with ovarian cancer.
- Published
- 2019
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