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292 results on '"Trusolino, Livio"'

2. XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients

Author

Leto, Simonetta M., Grassi, Elena, Avolio, Marco, Vurchio, Valentina, Cottino, Francesca, Ferri, Martina, Zanella, Eugenia R., Borgato, Sofia, Corti, Giorgio, di Blasio, Laura, Somale, Desiana, Vara-Messler, Marianela, Galimi, Francesco, Sassi, Francesco, Lupo, Barbara, Catalano, Irene, Pinnelli, Marika, Viviani, Marco, Sperti, Luca, Mellano, Alfredo, Ferrero, Alessandro, Zingaretti, Caterina C., Puliafito, Alberto, Primo, Luca, Bertotti, Andrea, and Trusolino, Livio

Published
2024
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4. Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer

Author

Malla, Sudhir B., Byrne, Ryan M., Lafarge, Maxime W., Corry, Shania M., Fisher, Natalie C., Tsantoulis, Petros K., Mills, Megan L., Ridgway, Rachel A., Lannagan, Tamsin R. M., Najumudeen, Arafath K., Gilroy, Kathryn L., Amirkhah, Raheleh, Maguire, Sarah L., Mulholland, Eoghan J., Belnoue-Davis, Hayley L., Grassi, Elena, Viviani, Marco, Rogan, Emily, Redmond, Keara L., Sakhnevych, Svetlana, McCooey, Aoife J., Bull, Courtney, Hoey, Emily, Sinevici, Nicoleta, Hall, Holly, Ahmaderaghi, Baharak, Domingo, Enric, Blake, Andrew, Richman, Susan D., Isella, Claudio, Miller, Crispin, Bertotti, Andrea, Trusolino, Livio, Loughrey, Maurice B., Kerr, Emma M., Tejpar, Sabine, Maughan, Timothy S., Lawler, Mark, Campbell, Andrew D., Leedham, Simon J., Koelzer, Viktor H., Sansom, Owen J., and Dunne, Philip D.

Published
2024
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6. Author Correction: Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer

Author

Malla, Sudhir B., Byrne, Ryan M., Lafarge, Maxime W., Corry, Shania M., Fisher, Natalie C., Tsantoulis, Petros K., Mills, Megan L., Ridgway, Rachel A., Lannagan, Tamsin R. M., Najumudeen, Arafath K., Gilroy, Kathryn L., Amirkhah, Raheleh, Maguire, Sarah L., Mulholland, Eoghan J., Belnoue-Davis, Hayley L., Grassi, Elena, Viviani, Marco, Rogan, Emily, Redmond, Keara L., Sakhnevych, Svetlana, McCooey, Aoife J., Bull, Courtney, Hoey, Emily, Sinevici, Nicoleta, Hall, Holly, Ahmaderaghi, Baharak, Domingo, Enric, Blake, Andrew, Richman, Susan D., Isella, Claudio, Miller, Crispin, Bertotti, Andrea, Trusolino, Livio, Loughrey, Maurice B., Kerr, Emma M., Tejpar, Sabine, Maughan, Timothy S., Lawler, Mark, Campbell, Andrew D., Leedham, Simon J., Koelzer, Viktor H., Sansom, Owen J., and Dunne, Philip D.

Published
2024
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7. Tolerance to colibactin correlates with homologous recombination proficiency and resistance to irinotecan in colorectal cancer cells

Author

Sogari, Alberto, Rovera, Emanuele, Grasso, Gaia, Mariella, Elisa, Reilly, Nicole Megan, Lamba, Simona, Mauri, Gianluca, Durinikova, Erika, Vitiello, Pietro Paolo, Lorenzato, Annalisa, Avolio, Marco, Piumatti, Eleonora, Bonoldi, Emanuela, Aquilano, Maria Costanza, Arena, Sabrina, Sartore-Bianchi, Andrea, Siena, Salvatore, Trusolino, Livio, Donalisio, Manuela, Russo, Mariangela, Di Nicolantonio, Federica, Lembo, David, and Bardelli, Alberto

Published
2024
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9. Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Author

Woo, Xing Yi, Giordano, Jessica, Srivastava, Anuj, Zhao, Zi-Ming, Lloyd, Michael W, de Bruijn, Roebi, Suh, Yun-Suhk, Patidar, Rajesh, Chen, Li, Scherer, Sandra, Bailey, Matthew H, Yang, Chieh-Hsiang, Cortes-Sanchez, Emilio, Xi, Yuanxin, Wang, Jing, Wickramasinghe, Jayamanna, Kossenkov, Andrew V, Rebecca, Vito W, Sun, Hua, Mashl, R Jay, Davies, Sherri R, Jeon, Ryan, Frech, Christian, Randjelovic, Jelena, Rosains, Jacqueline, Galimi, Francesco, Bertotti, Andrea, Lafferty, Adam, O’Farrell, Alice C, Modave, Elodie, Lambrechts, Diether, ter Brugge, Petra, Serra, Violeta, Marangoni, Elisabetta, El Botty, Rania, Kim, Hyunsoo, Kim, Jong-Il, Yang, Han-Kwang, Lee, Charles, Dean, Dennis A, Davis-Dusenbery, Brandi, Evrard, Yvonne A, Doroshow, James H, Welm, Alana L, Welm, Bryan E, Lewis, Michael T, Fang, Bingliang, Roth, Jack A, Meric-Bernstam, Funda, Herlyn, Meenhard, Davies, Michael A, Ding, Li, Li, Shunqiang, Govindan, Ramaswamy, Isella, Claudio, Moscow, Jeffrey A, Trusolino, Livio, Byrne, Annette T, Jonkers, Jos, Bult, Carol J, Medico, Enzo, and Chuang, Jeffrey H

Subjects
Cancer Genomics, Clinical Research, Genetics, Human Genome, Women's Health, Biotechnology, Cancer, Digestive Diseases, Good Health and Well Being, Animals, DNA Copy Number Variations, Databases, Genetic, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Metastasis, Polymorphism, Single Nucleotide, Exome Sequencing, Xenograft Model Antitumor Assays, PDXNET Consortium, EurOPDX Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.

Published
2021

11. Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia

Author

Gil Vazquez, Ester, Nasreddin, Nadia, Valbuena, Gabriel N., Mulholland, Eoghan J., Belnoue-Davis, Hayley L., Eggington, Holly R., Schenck, Ryan O., Wouters, Valérie M., Wirapati, Pratyaksha, Gilroy, Kathryn, Lannagan, Tamsin R.M., Flanagan, Dustin J., Najumudeen, Arafath K., Omwenga, Sulochana, McCorry, Amy M.B., Easton, Alistair, Koelzer, Viktor H., East, James E., Morton, Dion, Trusolino, Livio, Maughan, Timothy, Campbell, Andrew D., Loughrey, Maurice B., Dunne, Philip D., Tsantoulis, Petros, Huels, David J., Tejpar, Sabine, Sansom, Owen J., and Leedham, Simon J.

Published
2022
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14. Effective drug combinations in breast, colon and pancreatic cancer cells

Author

Jaaks, Patricia, Coker, Elizabeth A., Vis, Daniel J., Edwards, Olivia, Carpenter, Emma F., Leto, Simonetta M., Dwane, Lisa, Sassi, Francesco, Lightfoot, Howard, Barthorpe, Syd, van der Meer, Dieudonne, Yang, Wanjuan, Beck, Alexandra, Mironenko, Tatiana, Hall, Caitlin, Hall, James, Mali, Iman, Richardson, Laura, Tolley, Charlotte, Morris, James, Thomas, Frances, Lleshi, Ermira, Aben, Nanne, Benes, Cyril H., Bertotti, Andrea, Trusolino, Livio, Wessels, Lodewyk, and Garnett, Mathew J.

Published
2022
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15. Chromatin Velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin

Author

Tedesco, Martina, Giannese, Francesca, Lazarević, Dejan, Giansanti, Valentina, Rosano, Dalia, Monzani, Silvia, Catalano, Irene, Grassi, Elena, Zanella, Eugenia R., Botrugno, Oronza A., Morelli, Leonardo, Panina Bordignon, Paola, Caravagna, Giulio, Bertotti, Andrea, Martino, Gianvito, Aldrighetti, Luca, Pasqualato, Sebastiano, Trusolino, Livio, Cittaro, Davide, and Tonon, Giovanni

Published
2022
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16. The heme synthesis-export system regulates the tricarboxylic acid cycle flux and oxidative phosphorylation

Author

Fiorito, Veronica, Allocco, Anna Lucia, Petrillo, Sara, Gazzano, Elena, Torretta, Simone, Marchi, Saverio, Destefanis, Francesca, Pacelli, Consiglia, Audrito, Valentina, Provero, Paolo, Medico, Enzo, Chiabrando, Deborah, Porporato, Paolo Ettore, Cancelliere, Carlotta, Bardelli, Alberto, Trusolino, Livio, Capitanio, Nazzareno, Deaglio, Silvia, Altruda, Fiorella, Pinton, Paolo, Cardaci, Simone, Riganti, Chiara, and Tolosano, Emanuela

Published
2021
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17. PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models

Author

Meehan, Terrence F, Conte, Nathalie, Goldstein, Theodore, Inghirami, Giorgio, Murakami, Mark A, Brabetz, Sebastian, Gu, Zhiping, Wiser, Jeffrey A, Dunn, Patrick, Begley, Dale A, Krupke, Debra M, Bertotti, Andrea, Bruna, Alejandra, Brush, Matthew H, Byrne, Annette T, Caldas, Carlos, Christie, Amanda L, Clark, Dominic A, Dowst, Heidi, Dry, Jonathan R, Doroshow, James H, Duchamp, Olivier, Evrard, Yvonne A, Ferretti, Stephane, Frese, Kristopher K, Goodwin, Neal C, Greenawalt, Danielle, Haendel, Melissa A, Hermans, Els, Houghton, Peter J, Jonkers, Jos, Kemper, Kristel, Khor, Tin O, Lewis, Michael T, Lloyd, KC Kent, Mason, Jeremy, Medico, Enzo, Neuhauser, Steven B, Olson, James M, Peeper, Daniel S, Rueda, Oscar M, Seong, Je Kyung, Trusolino, Livio, Vinolo, Emilie, Wechsler-Reya, Robert J, Weinstock, David M, Welm, Alana, Weroha, S John, Amant, Frédéric, Pfister, Stefan M, Kool, Marcel, Parkinson, Helen, Butte, Atul J, and Bult, Carol J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, 2.6 Resources and infrastructure (aetiology), Good Health and Well Being, Animals, Databases as Topic, Disease Models, Animal, Humans, Mice, Neoplasms, Patients, Xenograft Model Antitumor Assays, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. Cancer Res; 77(21); e62-66. ©2017 AACR.

Published
2017

19. Long-term Clinical Outcome of Trastuzumab and Lapatinib for HER2-positive Metastatic Colorectal Cancer

Author

Tosi, Federica, Sartore-Bianchi, Andrea, Lonardi, Sara, Amatu, Alessio, Leone, Francesco, Ghezzi, Silvia, Martino, Cosimo, Bencardino, Katia, Bonazzina, Erica, Bergamo, Francesca, Fenocchio, Elisabetta, Martinelli, Erika, Troiani, Teresa, Siravegna, Giulia, Mauri, Gianluca, Torri, Valter, Marrapese, Giovanna, Valtorta, Emanuele, Cassingena, Andrea, Cappello, Giovanni, Bonoldi, Emanuela, Vanzulli, Angelo, Regge, Daniele, Ciardiello, Fortunato, Zagonel, Vittorina, Bardelli, Alberto, Trusolino, Livio, Marsoni, Silvia, and Siena, Salvatore

Published
2020
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20. Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling

Author

Ponsioen, Bas, Post, Jasmin B., Buissant des Amorie, Julian R., Laskaris, Dimitrios, van Ineveld, Ravian L., Kersten, Simone, Bertotti, Andrea, Sassi, Francesco, Sipieter, François, Cappe, Benjamin, Mertens, Sander, Verlaan-Klink, Ingrid, Boj, Sylvia F., Vries, Rob G. J., Rehmann, Holger, Vandenabeele, Peter, Riquet, Franck B., Trusolino, Livio, Bos, Johannes L., and Snippert, Hugo J. G.

Published
2021
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21. Adaptive mutability of colorectal cancers in response to targeted therapies

Author

Russo, Mariangela, Crisafulli, Giovanni, Sogari, Alberto, Reilly, Nicole M., Arena, Sabrina, Lamba, Simona, Bartolini, Alice, Amodio, Vito, Magrì, Alessandro, Novara, Luca, Sarotto, Ivana, Nagel, Zachary D., Piett, Cortt G., Amatu, Alessio, Sartore-Bianchi, Andrea, Siena, Salvatore, Bertotti, Andrea, Trusolino, Livio, Corigliano, Mattia, Gherardi, Marco, Lagomarsino, Marco Cosentino, Di Nicolantonio, Federica, and Bardelli, Alberto

Published
2019

22. Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial

Author

Sartore-Bianchi, Andrea, Lonardi, Sara, Martino, Cosimo, Fenocchio, Elisabetta, Tosi, Federica, Ghezzi, Silvia, Leone, Francesco, Bergamo, Francesca, Zagonel, Vittorina, Ciardiello, Fortunato, Ardizzoni, Andrea, Amatu, Alessio, Bencardino, Katia, Valtorta, Emanuele, Grassi, Elena, Torri, Valter, Bonoldi, Emanuela, Sapino, Anna, Vanzulli, Angelo, Regge, Daniele, Cappello, Giovanni, Bardelli, Alberto, Trusolino, Livio, Marsoni, Silvia, and Siena, Salvatore

Published
2020
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24. Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer

Author

Siravegna, Giulia, Lazzari, Luca, Crisafulli, Giovanni, Sartore-Bianchi, Andrea, Mussolin, Benedetta, Cassingena, Andrea, Martino, Cosimo, Lanman, Richard B., Nagy, Rebecca J., Fairclough, Stephen, Rospo, Giuseppe, Corti, Giorgio, Bartolini, Alice, Arcella, Pamela, Montone, Monica, Lodi, Francesca, Lorenzato, Annalisa, Vanzati, Alice, Valtorta, Emanuele, Cappello, Giovanni, Bertotti, Andrea, Lonardi, Sara, Zagonel, Vittorina, Leone, Francesco, Russo, Mariangela, Balsamo, Antonella, Truini, Mauro, Di Nicolantonio, Federica, Amatu, Alessio, Bonazzina, Erica, Ghezzi, Silvia, Regge, Daniele, Vanzulli, Angelo, Trusolino, Livio, Siena, Salvatore, Marsoni, Silvia, and Bardelli, Alberto

Published
2018
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25. Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens

Author

Behan, Fiona M., Iorio, Francesco, Picco, Gabriele, Gonçalves, Emanuel, Beaver, Charlotte M., Migliardi, Giorgia, Santos, Rita, Rao, Yanhua, Sassi, Francesco, Pinnelli, Marika, Ansari, Rizwan, Harper, Sarah, Jackson, David Adam, McRae, Rebecca, Pooley, Rachel, Wilkinson, Piers, van der Meer, Dieudonne, Dow, David, Buser-Doepner, Carolyn, Bertotti, Andrea, Trusolino, Livio, Stronach, Euan A., Saez-Rodriguez, Julio, Yusa, Kosuke, and Garnett, Mathew J.

Published
2019
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27. Innovations, challenges, and minimal information for standardization of humanized mice

Author

Stripecke, Renata, Münz, Christian, Schuringa, Jan Jacob, Bissig, Karl‐Dimiter, Soper, Brian, Meeham, Terrence, Yao, Li‐Chin, Di Santo, James P, Brehm, Michael, Rodriguez, Estefania, Wege, Anja Kathrin, Bonnet, Dominique, Guionaud, Silvia, Howard, Kristina E, Kitchen, Scott, Klein, Florian, Saeb‐Parsy, Kourosh, Sam, Johannes, Sharma, Amar Deep, Trumpp, Andreas, Trusolino, Livio, Bult, Carol, and Shultz, Leonard

Published
2020
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30. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial

Author

Sartore-Bianchi, Andrea, Trusolino, Livio, Martino, Cosimo, Bencardino, Katia, Lonardi, Sara, Bergamo, Francesca, Zagonel, Vittorina, Leone, Francesco, Depetris, Ilaria, Martinelli, Erika, Troiani, Teresa, Ciardiello, Fortunato, Racca, Patrizia, Bertotti, Andrea, Siravegna, Giulia, Torri, Valter, Amatu, Alessio, Ghezzi, Silvia, Marrapese, Giovanna, Palmeri, Laura, Valtorta, Emanuele, Cassingena, Andrea, Lauricella, Calogero, Vanzulli, Angelo, Regge, Daniele, Veronese, Silvio, Comoglio, Paolo M, Bardelli, Alberto, Marsoni, Silvia, and Siena, Salvatore

Published
2016
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31. Evolving neoantigen profiles in colorectal cancers with DNA repair defects

Author

Rospo, Giuseppe, Lorenzato, Annalisa, Amirouchene-Angelozzi, Nabil, Magrì, Alessandro, Cancelliere, Carlotta, Corti, Giorgio, Negrino, Carola, Amodio, Vito, Montone, Monica, Bartolini, Alice, Barault, Ludovic, Novara, Luca, Isella, Claudio, Medico, Enzo, Bertotti, Andrea, Trusolino, Livio, Germano, Giovanni, Di Nicolantonio, Federica, and Bardelli, Alberto

Published
2019
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37. Phosphoproteomics of patient-derived xenographs identifies targets and markers associated with sensitivity and resistance to EGFR blockade in colorectal cancer.

Author

Beekhof, Robin, Bertotti, Andrea, Böttger, Franziska, Vurchio, Valentina, Cottino, Francesca, Zanella, Eugenia R., Migliardi, Giorgia, Viviani, Marco, Grassi, Elena, Lupo, Barbara, Henneman, Alex A., Knol, Jaco C., Pham, Thang V., de Goeij-de Haas, Richard, Piersma, Sander R., Labots, Mariette, Verheul, Henk M.W., Trusolino, Livio, and Jimenez, Connie R.

Abstract

Epidermal growth factor receptor (EGFR) is a well-exploited therapeutic target in metastatic colorectal cancer (mCRC). Unfortunately, not all patients benefit from current EGFR inhibitors. Mass spectrometry–based proteomics and phosphoproteomics were performed on 30 genomically and pharmacologically characterized mCRC patient–derived xenografts (PDXs) to investigate the molecular basis of response to EGFR blockade and identify alternative drug targets to overcome resistance. Both the tyrosine and global phosphoproteome as well as the proteome harbored distinctive response signatures. We found that increased pathway activity related to mitogen-activated protein kinase (MAPK) inhibition and abundant tyrosine phosphorylation of cell junction proteins, such as CXADR and CLDN1/3, in sensitive tumors, whereas epithelial-mesenchymal transition and increased MAPK and AKT signaling were more prevalent in resistant tumors. Furthermore, the ranking of kinase activities in single samples confirmed the driver activity of ERBB2, EGFR, and MET in cetuximab-resistant tumors. This analysis also revealed high kinase activity of several members of the Src and ephrin kinase family in 2 CRC PDX models with genomically unexplained resistance. Inhibition of these hyperactive kinases, alone or in combination with cetuximab, resulted in growth inhibition of ex vivo PDX-derived organoids and in vivo PDXs. Together, these findings highlight the potential value of phosphoproteomics to improve our understanding of anti-EGFR treatment and response prediction in mCRC and bring to the forefront alternative drug targets in cetuximab-resistant tumors. Editor's summary: Epidermal growth factor receptor (EGFR)–targeted therapy is a common treatment for patients with metastatic colorectal cancer (mCRC); however, some patients fail to respond. Here, Beekhof et al. performed phosphoproteomics on a cohort of 30 patient-derived xenografts to identify non-genomic mechanisms of resistance and sensitivity. The authors found increased kinase activity in resistant tumors, including two models with unexplained genomic resistance. Inhibition of these kinases overcame resistance, highlighting the use of phosphoproteomics in identifying new drug targets for patients with mCRC. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Published
2023
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39. The genomic landscape of response to EGFR blockade in colorectal cancer

Author

Bertotti, Andrea, Papp, Eniko, Jones, Sian, Adleff, Vilmos, Anagnostou, Valsamo, Lupo, Barbara, Sausen, Mark, Phallen, Jillian, Hruban, Carolyn A., Tokheim, Collin, Niknafs, Noushin, Nesselbush, Monica, Lytle, Karli, Sassi, Francesco, Cottino, Francesca, Migliardi, Giorgia, Zanella, Eugenia R., Riberof, Dario, Russolillo, Nadia, Mellano, Alfredo, Muratore, Andrea, Paraluppi, Gianluca, Salizzoni, Mauro, Marsoni, Silvia, Kragh, Michael, Lantto, Johan, Cassingena, Andrea, Li, Qing Kay, Karchin, Rachel, Scharpf, Robert, Sartore-Bianchi, Andrea, Siena, Salvatore, Diaz, Jr., Luis A., Trusolino, Livio, and Velculescu, Victor E.

Subjects
Gene mutations -- Identification and classification -- Health aspects, Drug metabolism -- Genetic aspects, Colorectal cancer -- Genetic aspects -- Care and treatment, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Colorectal cancer is the third most common cancer worldwide, with 1.2 million patients diagnosed annually. In late-stage colorectal cancer, the most commonly used targeted therapies are the monoclonal antibodies cetuximab [...]

Published
2015

40. MicroRNA 483‐3p overexpression unleashes invasive growth of metastatic colorectal cancer via NDRG1 downregulation and ensuing activation of the ERBB3/AKT axis.

Author

Candiello, Ermes, Reato, Gigliola, Verginelli, Federica, Gambardella, Gennaro, D′Ambrosio, Antonio, Calandra, Noemi, Orzan, Francesca, Iuliano, Antonella, Albano, Raffaella, Sassi, Francesco, Luraghi, Paolo, Comoglio, Paolo M., Bertotti, Andrea, Trusolino, Livio, and Boccaccio, Carla

Abstract

In colorectal cancer, the mechanisms underlying tumor aggressiveness require further elucidation. Taking advantage of a large panel of human metastatic colorectal cancer xenografts and matched stem‐like cell cultures (m‐colospheres), here we show that the overexpression of microRNA 483‐3p (miRNA‐483‐3p; also known as MIR‐483‐3p), encoded by a frequently amplified gene locus, confers an aggressive phenotype. In m‐colospheres, endogenous or ectopic miRNA‐483‐3p overexpression increased proliferative response, invasiveness, stem cell frequency, and resistance to differentiation. Transcriptomic analyses and functional validation found that miRNA‐483‐3p directly targets NDRG1, known as a metastasis suppressor involved in EGFR family downregulation. Mechanistically, miRNA‐483‐3p overexpression induced the signaling pathway triggered by ERBB3, including AKT and GSK3β, and led to the activation of transcription factors regulating epithelial–mesenchymal transition (EMT). Consistently, treatment with selective anti‐ERBB3 antibodies counteracted the invasive growth of miRNA‐483‐3p‐overexpressing m‐colospheres. In human colorectal tumors, miRNA‐483‐3p expression inversely correlated with NDRG1 and directly correlated with EMT transcription factor expression and poor prognosis. These results unveil a previously unrecognized link between miRNA‐483‐3p, NDRG1, and ERBB3‐AKT signaling that can directly support colorectal cancer invasion and is amenable to therapeutic targeting. [ABSTRACT FROM AUTHOR]

Published
2023
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41. CONNECTOR, fitting and clustering of longitudinal data to reveal a new risk stratification system.

Author

Pernice, Simone, Sirovich, Roberta, Grassi, Elena, Viviani, Marco, Ferri, Martina, Sassi, Francesco, Alessandrì, Luca, Tortarolo, Dora, Calogero, Raffaele A, Trusolino, Livio, Bertotti, Andrea, Beccuti, Marco, Olivero, Martina, and Cordero, Francesca

Subjects
PANEL analysis, MOLECULAR association, COLORECTAL cancer, TUMOR growth, DYNAMICAL systems
Abstract

Motivation The transition from evaluating a single time point to examining the entire dynamic evolution of a system is possible only in the presence of the proper framework. The strong variability of dynamic evolution makes the definition of an explanatory procedure for data fitting and clustering challenging. Results We developed CONNECTOR, a data-driven framework able to analyze and inspect longitudinal data in a straightforward and revealing way. When used to analyze tumor growth kinetics over time in 1599 patient-derived xenograft growth curves from ovarian and colorectal cancers, CONNECTOR allowed the aggregation of time-series data through an unsupervised approach in informative clusters. We give a new perspective of mechanism interpretation, specifically, we define novel model aggregations and we identify unanticipated molecular associations with response to clinically approved therapies. Availability and implementation CONNECTOR is freely available under GNU GPL license at https://qbioturin.github.io/connector and https://doi.org/10.17504/protocols.io.8epv56e74g1b/v1. [ABSTRACT FROM AUTHOR]

Published
2023
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46. Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice

Author

Casazza, Andrea, Finisguerra, Veronica, Capparuccia, Lorena, Camperi, Andrea, Swiercz, Jakub M., Rizzolio, Sabrina, Rolny, Charlotte, Christensen, Claus, Bertotti, Andrea, Sarotto, Ivana, Risio, Mauro, Trusolino, Livio, Weitz, Jurgen, Schneider, Martin, Mazzone, Massimilano, Comoglio, Paolo M., and Tamagnone, Luca

Subjects
Cancer invasiveness -- Development and progression -- Genetic aspects, Metastasis -- Development and progression -- Genetic aspects, Cellular signal transduction -- Genetic aspects, Cancer cells -- Genetic aspects, Semaphorins -- Properties -- Genetic aspects, Health care industry
Abstract

Semaphorin 3E (Sema3E) is a secreted molecule implicated in axonal path finding and inhibition of developmental and postischemic angiogenesis. Sema3E is also highly expressed in metastatic cancer cells, but its mechanistic role in tumor progression was not understood. Here we show that expression of Sema3E and its receptor Plexin D1 correlates with the metastatic progression of human tumors. Consistent with the clinical data, knocking down endogenous expression of either Sema3E or Plexin D1 in human metastatic carcinoma cells hampered their metastatic potential when injected into mice, while tumor growth was not markedly affected. Conversely, overexpression of exogenous Sema3E in cancer cells increased their invasiveness, transendothelial migration, and metastatic spreading, although it inhibited tumor vessel formation, resulting in reduced tumor growth in mice. The proinvasive and metastatic activity of Sema3E in tumor cells was dependent on transactivation of the Plexin D1-associated ErbB2/Neu oncogenic kinase. In sum, Sema3E-Plexin D1 signaling in cancer cells is crucially implicated in their metastatic behavior and may therefore be a promising target for strategies aimed at blocking tumor metastasis., Introduction Semaphorins are secreted and membrane-bound signals, originally implicated in the control of axonal wiring (1). They comprise a wide protein family and are involved in a range of functions, [...]

Published
2010
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48. MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients

Author

Rocci, Alberto, Gambella, Manuela, Aschero, Simona, Baldi, Ileana, Trusolino, Livio, Cavallo, Federica, Gay, Francesca, Larocca, Alessandra, Magarotto, Valeria, Omedè, Paola, Isaia, Gianluca, Bertotti, Andrea, Liberati, Anna M., Catalano, Lucio, De Rosa, Luca, Musto, Pellegrino, Vallone, Roberto, Falcone, Antonietta, Drandi, Daniela, Ladetto, Marco, Comoglio, Paolo M., Boccadoro, Mario, and Palumbo, Antonio

Published
2014
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