• Istituto di Biologia e Patologia Molecolari

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Senior Researcher

Istitute of Molecular Biology and Pathology - National Research Council
Department of Molecular Medicine, Sapienza University of Rome , Viale Regina Elena 291, 00161 Rome, Italy
Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144 Rome, Italy

Our research focus on signaling components and determinants of membrane actin-based, motility machineries needed for the correct execution of invasive and metastatic programs in cancer. The invasion of cancer cells through the basement membrane might involve the formation of actin-based protrusions, invadopodia, as hubs of adhesive, proteolityc and cytoskeletal signaling pathways. Growth factor receptor activation might cause the engagement of integrins and associated proteins in invadopodia to coordinate extracellular matrix proteolytic degradation and invasive process. These processes are influenced by a dynamic reciprocity of cancer cells with surrounding stromal cells, which will feedback and further stimulate mechanosignaling, where invadopodia might act as mechanosensing structures. We have found that the G-protein coupled receptors, such as the endothelin-1 receptor (ET-1R), might drives cancer metastasis and invadopodia through the scaffolding function of β-arrestin1 (β-arr1). In ongoing projects we investigate:

1. new signaling pathways guided by β-arr1 in driving invasive process, dictating invadopodia formation and ECM degradation and the dynamic reciprocity and reinforcement of mechanosignaling between cancer cells and cancer-associated fibroblasts.
2. the feasibility of co-targeting these pathways for controlling invadopodia activity and metastatic dissemination in organotypic models and in xenografts.
  1. Tocci P, Cianfrocca R, Di Castro V, Rosanò L, Sacconi A, Donzelli S, Bonfiglio S, Bucci G, Vizza E, Ferrandina G, Scambia G, Tonon G, Blandino G, Bagnato A. β-arrestin1/YAP/mutant p53 complexes orchestrate the endothelin A receptor signaling in high-grade serous ovarian cancer. Nat Commun. 2019 Jul 19;10(1):3196. doi: 10.1038/s41467-019-11045-8. 
  2. Rosanò L, Bagnato A. New insights into the regulation of the actin cytoskeleton dynamics by GPCR/β-arrestin in cancer invasion and metastasis. Int Rev Cell Mol Biol. 2019;346:129-155. doi: 10.1016/bs.ircmb.2019.03.002. PubMed PMID: 31122393.
  3. Rosanò L, Cianfrocca R, Bagnato A. Methods to Investigate β-Arrestin-1/β-Catenin Signaling in Ovarian Cancer Cells. Methods Mol Biol. 2019;1957:393-406. doi: 10.1007/978-1-4939-9158-7_25. PubMed PMID: 30919368.
  4. Bagnato A, Rosanò L. New Routes in GPCR/β-Arrestin-Driven Signaling in Cancer  Progression and Metastasis. Front Pharmacol. 2019 Feb 19;10:114. doi: 10.3389/fphar.2019.00114. eCollection 2019. 
  5. Chellini L, Caprara V, Spadaro F, Sestito R, Bagnato A, Rosanò L. Regulation of extracellular matrix degradation and metastatic spread by IQGAP1 through endothelin-1 receptor signalling in ovarian cancer. Matrix Biol. 2018 Oct 25. pii: S0945-053X(18)30303-2. doi: 10.1016/j.matbio.2018.10.005. [Epub ahead of print] PubMed PMID: 30367951.   
  6. Di Modugno F, Caprara V, Chellini L, Tocci P, Spadaro F, Ferrandina G, Sacconi A, Blandino G, Nisticò P, Bagnato A, Rosanò L. hMENA is a key regulator in endothelin-1/β-arrestin1-induced invadopodial function and metastatic process. Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3132-3137.
  7. Semprucci E, Tocci P, Cianfrocca R, Sestito R, Caprara V, Veglione M, Castro VD, Spadaro F, Ferrandina G, Bagnato A, Rosanò L. Endothelin A receptor drives invadopodia function and cell motility through the β-arrestin/PDZ-RhoGEF pathway  in ovarian carcinoma. Oncogene. 2016 Jun 30;35(26):3432-42.
  8. Rosanò L, Cianfrocca R, Tocci P, Spinella F, Di Castro V, Caprara V, Semprucci E, Ferrandina G, Natali PG, Bagnato A. Endothelin A receptor/β-arrestin signaling to the Wnt pathway renders ovarian cancer cells resistant to chemotherapy. Cancer Res. 2014 Dec 15;74(24):7453-64.
  9. Rosanò L, Spinella F, Bagnato A. Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2013 Sep;13(9):637-51. 
  10. Rosanò L, Cianfrocca R, Tocci P, Spinella F, Di Castro V, Spadaro F, Salvati E, Biroccio AM, Natali PG, Bagnato A. β-arrestin-1 is a nuclear transcriptional regulator of endothelin-1-induced β-catenin signaling. Oncogene. 2013 Oct 17;32(42):5066-77. 
  11. Rosanò L, Cianfrocca R, Spinella F, Di Castro V, Nicotra MR, Lucidi A, Ferrandina G, Natali PG, Bagnato A. Acquisition of chemoresistance and EMT phenotype is linked with activation of the endothelin A receptor pathway in ovarian carcinoma cells. Clin Cancer Res. 2011 Apr 15;17(8):2350-60. 
  12.  Rosanò L, Cianfrocca R, Masi S, Spinella F, Di Castro V, Biroccio A, Salvati  E, Nicotra MR, Natali PG, Bagnato A. Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2806-11.



H-index =33  citations= 3405 (Scopus)

Ilenia Masi, PhD student
Valentina Caprara, Tecnhician
Dr. Anna Bagnato, Istituto Regina Elena, Roma
Prof. Gabriella Ferrandina, Ginecologia Oncologica, Università Cattolica di Roma  
Prof. Alberto Rainer, Laboratorio di Ingegneria Tissutale,  Università Campus Bio-Medico di Roma  
Dr.ssa Francesca Spadaro, Unità di Microscopia Confocale, Istituto Superiore di Sanità
Prof. Ernst Lengyel, Department of Obstetrics and Gynecology, University of Chicago
Dr. Albiges-Rizo Corinne, Institut Albert Bonniot Centre de recherche UGA/Inserm U1209 / CNRS UMR, Grenoble
2017 National Scientific Qualification. Prima Fascia 06/A2 - Patologia Generale e Patologia Clinica; Prima Fascia 05/F1 - Biologia Applicata
1998-2002 Resident, School of Specialization in Clinical Pathology, Faculty of Medicine and Surgery, University "La Sapienza" Roma. 
1995 Degree in Biological Science, University "La Sapienza" Roma 
2018-20122 Principal Investigator, AIRC Grant: Dynamic signaling reciprocity shapes invadopodia function and metastatic process of ovarian cancer: role of endothelin-1
2018 Principal Investigator, Progetti Complessi Interdipartimentali IRE: Identificazione del network di segnali del matrisoma nel processo metastatico del carcinoma ovarico: il ruolo dei recettori dell’endotelina nel microambiente tumorale.
30/11/2018-Today Researcher in staff at IBPM Institute of Molecular Biology and Pathology- CNR National Research Council of Italy
2013-29/11/2018 Senior Research Contract “5x1000 IRE”, Regina Elena National Cancer Institute of Rome 
02/2017-03/2017 Visiting Scientist UCL, Faculty of Medical Sciences, Division of Surgery and Interventional Science, London, UK (Prof. Marilena Loizidou, Head of Research Department of Nanotechnology)
2016-2018 Principal Investigator, AIRC Grant “Endothelin axis/?-arrestin-driven actin reorganization: bringing the right network of proteins to direct invadopodia ”.
2013-2015 Principal Investigator, AIRC Grant “Role of beta-arrestin as a multifunctional adapter of G protein coupled receptor-driven tumor cell motility”.
2009-2012 Senior Research Contract AIRC Grant, PI Dr. Anna Bagnato, Laboratory of Molecular Pathology and Ultrastructure, Regina Elena National Cancer Institute of Rome
2007-2008 PI Research Fellow “New Idea Award Ricerca Corrente 2006”, Regina Elena National Cancer Institute of Rome
2003-2006 Senior Research Contract AIRC Grant, PI Dr. Anna Bagnato, Laboratory of Molecular Pathology and Ultrastructure, Regina Elena National Cancer Institute of Rome
2000-2002 Competitive Research Fellow FIRC, Laboratory of Molecular Pathology and Ultrastructure, Regina Elena National Cancer Institute of Rome
1998-1999 Young Research Contract AIRC Grant, PI Dr. Anna Bagnato, Laboratory of Molecular Pathology and Ultrastructure, Regina Elena National Cancer Institute of Rome
1996-1997 Young Research Fellow “Ministero della Salute”, PI Dr. Alberto Chersi, Laboratory of Biochemistry, Regina Elena National Cancer Institute of Rome
1994-1995 Internship, Laboratory of Human Genetics, Dept. of Genetics and Molecular Biology, University "La Sapienza" Rome (Prof. Rosaria Scozzari)
2010 Recipient of “PREMIO ELENA CAPPANNINI 2010” at 52th Annual Meeting of the Italian Cancer Society (SIC) for the best publication (ß-Arrestin links endothelin A receptor to ß-catenin signaling to induce ovarian cancer cell invasion and metastasis - Proc Natl Acad Sci U S A. 106: 2806-11, 2009).
2006 Poster awarded from Pezcoller-Bedogni  Foundation, at 18th Pezcoller Symposium “Tumor microenvironment: heterotypic interactions”,  Trento, June 27-29, 2006.
2005-2007 Principal Investigator, U.O. IRE, Regional Grant  AIRC “Mechanism and circumvention of chemotherapy resistance in ovarian cancer”.
2005 AACR-Pezcoller Foundation Scholar-in-Training Award at AACR 95th Annual Meeting.
2005 Fondazione Guido Berlucchi Award for Italian young researcher 
2004 Best Poster Award from Nature Review Cancer at  “Cadherins, Catenins and Cancer”, Madrid, November 19-December 1, 2004.
2000 Recipient of  “Premio Trivella” at XV Meeting of Italian Society of Cancer Research.
2015-today Grant reviewer for The Centre National de la Recherche Scientifique (CNRS)-France
Wellbeing of Women-UK