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Thomas Jefferson University - Andrea Morrione, PhD
Andrea Morrione, PhD

Urology
Research Associate Professor
Director of Urology Research
Department of Urology
Kimmel Cancer Center
Biology of Prostate Cancer Program
Mailing Address
620 BLSB , 233 South 10th Street
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-4519
Fax: 215-923-0249
andrea.morrione@jefferson.edu
Qualifications
1992: Ph.D., University of Milan, Italy, Biological Sciences.
1992-1993: Research Fellow, Biochemistry, University of Milan, Italy.
1993-1997: Post-Doctoral Fellow, Department of Microbiology and Immunology,
Thomas Jefferson University in the laboratory of Dr. Renato Baserga.
Expertise and Research Interests
1) Progranulin (also known as proepithelin, granulin-epithelin precursor, PCDGF or acrogranin) is a secreted pluripotent growth factor that plays a significant role in cell proliferation and cell cycle progression in many cellular systems. Progranulin is highly expressed in several aggressive tumors, where the malignancy grade correlates with its expression levels. Progranulin is also promoting cell migration, and it is important in wound healing and tissue repair. Given its critical role in wound repair and cancer progression, proepithelin may prove a useful clinical target for prognosis and therapy. Despite the strong connections with growth control and cancer, proepithelins mode of action is not well understood. Furthermore, the progranulin receptor and/or proteins that mediate the early stages of progranulin signaling from the plasma membrane have not been identified.
We are now investigating the role of progranulin and novel membrane progranulin-interacting proteins, which we hypothesize are either the progranulin receptor or proteins involved in progranulin signaling, in proliferation, migration and transformation of bladder and prostate cancer cells.

2) The tyrosine kinase type 1 insulin-like growth factor receptor (IGF-IR) plays a significant role in a variety of cellular processes including mitogenesis, differentiation and increased cell motility. Aberrant IGF-IR signaling contributes toward tumor progression through its antiapoptotic action and the induction of prometastatic pathways. Targeted depletion of the IGF-IR reverses the transforming phenotype and sensitizes cells to anticancer treatments in several cancer cell models, suggesting that the IGF-IR plays a broad role in cancer.
We have recenrly determined the role of the IGF-IR in bladder cancer.
We demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues compared to non-malignant controls. We have investigated the role of the IGF-IR in bladder cancer using urothelial carcinoma-derived 5637 and T24 cells. Although activation of the IGF-IR did not appreciably affect their growth, it did promote migration and stimulate in vitro wound closure and invasion. These effects required the activation of the Akt and MAPK pathways and IGF-I induced Akt- and MAPK-dependent phosphorylation of paxillin, which relocated at dynamic focal adhesions and it was necessary for promoting motility in bladder cancer cells.
Additionally,we have recently characterize Pyk2 funcition in urothelial cancer cells and shown that Pyk2 is critical in regulating IGF-IR-dependent motility and signaling of invasive urothelial cancer cells.
Our results support the hypothesis that the IGF-IR may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia. The IGF-IR and Pyk2 may also serve as novel biomarkers for bladder cancer.
More recent projects include the characterization of the IR and IGF-IR cross-talk to DDR1 and bladder cancer progression.

3)The adaptor protein Grb10 interacts with the IGF-IR in a ligand-dependent manner serving as an important regulator of IGF-IR signaling. Grb10 functions as an adaptor protein by binding the E3 ubiquitin ligase Nedd4 serving to bring the ligase into close proximity to the IGF-IR such that ubiquitination occurs upon ligand stimulation. The ubiquitinated IGF-IR is subsequently targeted for degradation, giving rise to long-term attenuation of signaling, a process known as down-regulation. However, the precise molecular details by which Grb10 and Nedd4 serve to contribute to down-regulation of the IGF-IR remain poorly understood. We have recently shown that Grb10/Nedd4complex mediates multiubiquitination (monoubiquitination at multiple sites) of the IGF-IR, which is required for receptor internalization in clathrin-dependent and independent pathways. We are now focusing on the identification of novel proteins involved in IGF-IR sorting/recycling.

Other Expertise
Cell signaling
cell transformation
bladder cancer
growth factors and growth factor receptors
Keywords
Progranulin; Bladder Cancer; Prostate cancer; Cell Biology; Cell Signaling; Endocytosis; Grb10; IGF-IR; IR; Migration; Mouse Embryo Fibroblasts; Nedd4; Proepithelin; Sorting; Ubiquitination; Urology; invasion; wound healing
Languages
English
Italian
Publications
  • Marco Vanoni, Marina Vai, Andrea Morrione, Marina Venturini, Emanuela LacanĂ , Enzo Martegani, Laura Popolo and Lilia Alberghina: Sequences promoting and preventing excretion in the growth medium of homologous and heterologous proteins in Saccharomyces cerevisiae. ECB6: Proceedings of the 6th European Congress on Biotechnology, 143-146, 1993.
  • Andrea Morrione, Tiziana DeAngelis and Renato Baserga: The GC factor regulates the expression of the Insulin-like Growth Factor 1 receptor. Cell Proliferation. 28:659-671, 1995.
  • Andrea Morrione, Tiziana DeAngelis and Renato Baserga: Failure of the bovine papilloma virus to transform mouse embryo fibroblast with a targeted disruption of the IGF-I Receptor Genes. Journal of Virology, vol. 69, 6:5300-5303, 1995
  • Consuelo D'Ambrosio, Susanne R. Keller, Andrea Morrione, Gustav E. Lienhard, Renato Baserga and Ewa Surmacz: Transforming Potential of the Insulin Receptor Substrate. Cell Growth and Differentiation 6:557-562, 1995.
  • Atsushi Hongo, Consuelo D'Ambrosio, Masahiko Miura, Andrea Morrione and Renato Baserga: Mutational Analysis and Transforming Activities of the Insulin-Like Growth Factor I Receptor. Oncogene 12:1231-1238, 1996.
  • Andrea Morrione, Barbara Valentinis, Shiwei Li, James Y. T. Ooi, Ben Margolis and Renato Baserga: Grb10: a new substrate of the Insulin-like Growth Factor Receptor I. Cancer Research 56:3165-3167, 1996.
  • Marina Venturini, Andrea Morrione, Patrizia Pisarra, Enzo Martegani and Marco Vanoni: In Saccharomyces cerevisiae a short amino acid sequence facilitates excretion in the growth medium of periplasmic proteins. Molecular Microbiology 23 (5) 997-1007, 1997.
  • Andrea Morrione, Barbara Valentinis, Shi-Qiong Xu, Gladys Yumet, Angeliki Louvi, Argiris Efstratiadis and Renato Baserga: IGF-II Stimulates Cell Proliferation through the Insulin Receptor. Proceedings of the National Academy of Sciences, U.S.A. 94:3777-3782, 1997.
  • Barbara Valentinis, Andrea Morrione, Stephen Taylor and Renato Baserga: IGF-I Receptor Signaling in Transformation by src Oncogenes. Molecular and Cellular Biology 17:3744-3754, 1997.
  • Andrea Morrione, Barbara Valentinis, Mariana Resnicoff, Shi-Qiong Xu and Renato Baserga: The Role of mGrb10a in IGF-I-Mediated Growth. Journal of Biological Chemistry 272:26382-26387, 1997.
  • Renato Baserga, Andrea Morrione, and Marco Prisco: Growth Factors, Cell Proliferation, and Apoptosis. Heart Failure Reviews 3, 5-14, 1998.
  • Barbara Valentinis, Andrea Morrione, Francesca Peruzzi, Krzysztof Reiss, RenatoBaserga: Anti-apoptotic Singaling of the IGF-I Receptor in Fibroblasts Following Loss of Matrix Adhesion. Oncogene 18:1827-1836, 1999.
  • Barbara Valentinis, Gaetano Romano, Francesca Peruzzi, Andrea Morrione, Marco Prisco, Silvia Soddu, Barbara Cristofanelli, Ada Sacchi and Renato Baserga: Growth and Differentiation Signals by the Insulin-like Growth Factor 1 Receptor in Hemopoietic Cells Are Mediated through Different Pathways. Journal of Biological Chemistry 274:12423-12430, 1999.
  • Andrea Morrione, Pamela Plant, Barbara Valentinis, Oliver Staub, Daniela Rotin, Sharad Kumar and Renato Baserga: mGrb10 interacts with Nedd4. Journal of Biological Chemistry 274:24094-24099, 1999.
  • Krzysztof Reiss, Gladys Yumet, Simei Shan, Ziwei Huang, Emad Alnemri, Srinivasa M. Srinivasula, Jin-Ying Wang, Andrea Morrione and Renato Baserga: A Synthetic Peptide Sequence from the C-Terminus of the IGF-I Receptor that induces Apoptosis and Inhibition of Tumor Growth. Journal of Cellular Physiology 181:124-135, 1999.
  • Renato Baserga and Andrea Morrione: Differentiation and Malignant Transformation: Two Roads Diverged in a Wood. Journal of Cellular Biochemistry, 32/33:68-75, 1999.
  • Andrea Morrione. Grb10 proteins in insulin-like growth factor and insulin receptor signaling. International Journal of Molecular Medicine. International Journal of Molecular Medicine 5:151-154, 2000.
  • Andrea Morrione, Gaetano Romano, Magali Navarro, Krzysztof Reiss, Barbara Valentinis, Michael Dews, Eva Eves, Marsha Rich Rosner, and Renato Baserga. Insulin-like Growth Factor-1 Receptor Signaling in Differentiation of Neuronal H19-7 Cells. Cancer Research 60:2263-2272, 2000.
  • Michael Dews, Marco Prisco, Francesca Peruzzi, Gaetano Romano, Andrea Morrione and Renato Baserga: Domains of the IGF-I Receptor Required for the Activation of Extracellular Signal-Regulated Kinases. Endocrinology 141:1289-1300, 2000.
  • Krzysztof Reiss, Jin-Ying Wang, Gaetano Romano, Frank B. Furnari, Webster K. Cavenee, Andrea Morrione, Xiao Tu and Renato Baserga: IGF-I receptor signaling in a prostate cancer cell line with a PTEN mutation. Oncogene19: 2687-2694, 2000.
  • Barbara Valentinis, Magali Navarro, Tommaso Zanocco-Marani, Pamela Edmonds, Jason McCormick, Andrea Morrione, Ada Sacchi, Gaetano Romano, Krzysztof Reiss and Renato Baserga: Insulin Receptor Substrate-1, p70S6K and Cell Size in Transformation and Differentiation of Hemopoietic Cells. Journal of Biological Chemistry 275: 25451-25459, 2000.
  • Slupianek, M. Nieborowska-Skorska, G. Hoser, A. Morrione, M. Majewski, L. Xue, S. W. Morris, M. A. Wasik, and T. Skorski. Role of PI-3k-Akt pathway in NPM/ALK-mediated lymphomagenesis. Cancer Research. 61:2194-2199, 2001.
  • Barbara Belletti, Marco Prisco, Andrea Morrione, Barbara Valentinis, Magali Navarro and Renato Baserga. Regulation of Id2 Gene Expression by the IGF-I Receptor Requires Signaling by Phosphatidylinositol-3 Kinase. Journal of Biological Chemistry. 276: 13867-13874, 2001.
  • Andrea Morrione, Magali Navarro, Gaetano Romano, Michael Dews, Krzysztof Reiss, Barbara Valentinis, Barbara Belletti and Renato Baserga: The Role of the Insulin Receptor Substrate-1 in the Differentiation of Rat Hippocampal Neuronal Cells. Oncogene. 20: 4842-4852, 2001.
  • Francesca Peruzzi, Marco Prisco, Andrea Morrione, Barbara Valentinis and Renato Baserga: Anti-apoptotic Signaling of the IGF-I Receptor by Mitochondrial translocation of c-Raf and Nedd4. Journal of Biological Chemistry. 276: 25990-25996, 2001.
  • Barbara Belletti, Robert Drakas, Andrea Morrione, Xiao Tu, Ivan Casaburi and Renato Baserga: Regulation of ID1 Protein Expression in Mouse Embryo Fibroblasts by the Type 1 Insulin-Like Growth Factor Receptor. Experimental Cell Research. 277: 107-118, 2002.
  • Agata Klejman, Lori Rushen,Andrea Morrione, Artur Slupianel and Tomasz Skorski: Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571. Oncogene. 21: 5868-5876, 2002.
  • Andrea Vecchione, Adriano Marchese, Pauline Henry, Daniela Rotin and Andrea Morrione: The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the IGF-I Receptor. Molecular and Cellular Biology. 23 3363-3372, 2003.
  • Andrea Morrione. Grb10 adapter protein as regulator of Insulin-like Growth Factor Receptor Signaling. Journal of Cellular Physiology. 197. 307-311, 2003.
  • Gustavo Baldassarre, Barbara Belletti, Milena Nicoloso, Monica Schiappacassi, Andrea Vecchione, Paola Spessotto, Andrea Morrione, Vincenzo Cerami, and Alfonso Colombatti: p27Kip1-stathmin interaction influences sarcoma cell migration and invasion. Cancer Cell. 7 51-63, 2005.
  • Shu-yue Ren, Elizabeth Bolton, M. Golam Mohi, Andrea Morrione, Benjamin G. Neel, and Tomasz Skorski: Phosphatidylinositol 3-kinase p85a subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequences. Molecular and Cellular Biology. 25(18) 8001-8008, 2005.
  • Giada Monami, Eva M. Gonzalez,Michelle Hellman, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo and Andrea Morrione: Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex. Cancer Research. 66(14)7103-7110, 2006.
  • Giada Monami, Velia Emiliozzi and Andrea Morrione: Grb10-/Nedd4-mediated multiubiquitination of the Insulin-Like Growth Factor Receptor regulates receptor internalization. Journal of Cellular Physiology. 216 426-437, 2008.
  • Andrea Vecchione, Matteo Fassan, Andrea Morrione, Silvia Goldoni, Gustavo Baldassarre, Dolores Byrne, Domenico D'arca, Juan Palazzo, J Lloyd, V Anesti, Luca Scorrano, Leonard G. Gomella, Renato V. Iozzo, Raffaele Baffa: Mitostatin, a Novel Mitochondrial Putative Tumor Suppressor Gene on Human Chromosome 12Q24.1, is Down-Regulated in Bladder and Breast Cancers. Oncogene. 2008 Jan 15;28(2):257-69.
  • Giada Monami, Velia Emiliozzi, Alessandro Bitto, Francesca Lovat, Xi-Qiong Xu, Silvia Goldoni, Matteo Fassan, Ginette Serrero, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo and Andrea Morrione: Proepithelin Regulates Prostate Cancer cell Biology by Promoting Cell Growth, Migration and Anchorage-independent Growth. The American Journal of Pathology. 2009 Mar;174(3):1037-47.
  • Francesca Lovat, Alessandro Bitto, Shi-Qiong Xu, Matteo Fassan, David Metalli, Vera Wubah, Silvia Goldoni, Peter McCue, Ginette Serrero, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo and Andrea Morrione: Proepithelin is an autocrine growth factor for bladder cancer. Carcinogenesis. 2009 May;30(5):861-8.
  • David Metalli, Francesca Lovat, Farida Tripodi, Marco Genua,Shi-Qiong Xu, Michela Spinelli, Lilia Alberghina, Marco Vanoni, Leonard G. Gomella, Renato V. Iozzo and Andrea Morrione: The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells Through Akt- and Mitogen-Activated Protein Kinase-Dependent activation of Paxillin. The America Journal of Pathology. 2010 Jun;176(6):2997-3006.
  • Tiziana DeAngelis, Andrea Morrione and Renato Baserga: Mutual Interaction and Reciprocal Down-regulation between c-met and Insulin Receptor Substrate-1. Journal of Cellular Physiology. 2010 Sep;224(3):658-63.
  • Matteo Fassan, Domenico DArca, Juraj Letko, Andrea Vecchione, Marina P. Gardiman, Peter McCue, Bernadette Wildemore, Massimo Rugge, Dolores Shupp-Byrne, Leonard G. Gomella, Andrea Morrione, Renato V. Iozzo and Raffaele Baffa: Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells. PLoS ONE. 2011 May 6;6(5):e19771.
  • Elena Sacco, David Metalli, Michela Spinelli, Romilde Manzoni, Maria Samalikova, Andrea Morrione, Silvio Traversa, Lilia Alberghina, and Marco Vanoni. Novel RasGRF1-derived Tat-fused peptides inhibiting Ras-dependent proliferation and migration in mouse and human cancer cells. Biotechnology Advances. Biotechnology Advances. 2011 May 18. [Epub ahead of print]
  • Renato V. Iozzo, Simone Buraschi, Marco Genua, Shi-Qiong Xu, Charalambos C. Solomides, Stephen C. Peiper, Leonard G. Gomella, Rick C. Owens and Andrea Morrione. Decorin Antagonizes IGF-IR Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling. Journal of Biological Chemistry. 2011 Oct 7;286(40):34712-21.
  • Alaide Morcavallo, Marco Genua, Angela Palummo, Jiri Jiracek, Andrzej M. Brzozowski, Renato V. Iozzo, Antonino Belfiore and Andrea Morrione. Insulin and Insulin-like Growth Factor II differentially regulate endocytic sorting and stability of the Insulin Receptor Isoform A. Journal of Biological Chemistry. 287, NO. 14, pp. 1142211436.
  • Marco Genua, Shi-Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonino Belfiore, Renato V. Iozzo and Andrea Morrione. Proline-Rich Tyrosine Kinase 2 (Pyk2) Regulates IGF-I-induced Cell Motility and Invasion of Urothelial Carcinoma-derived Cells. PLoS ONE. PLoS One. 2012;7(6):e40148. Epub 2012 Jun 28.
  • Tiziana DeAngelis, Andrew Quong, Andrea Morrione and Renato Baserga. Growth of V-SRC-transformed cells in Serum-free medium through the induction of growth factors Journal of Cellular Physiology. 2012 Dec 18. doi: 10.1002/jcp.24303.
  • Hira Lal Goel , Aejaz Sayeed, Michael Breen, Matthew J. Zarif, David S. Garlick, Irwin Leav, Roger J. Davis, Thomas J. FitzGerald, Andrea Morrione, Chung-Cheng Hsieh, Qin Liu, Adam P. Dicker, Dario C. Altieri and Lucia R. Languino* beta1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase1. Journal of Cellular Physiology. In press.
  • Andrea Morrione, Thomas Neill and Renato V. Iozzo. Dichotomy of decorin activity on the insulin-like growth factor-I system. FEBSJ. In press.
  • Alaide Morcavallo, Simone Buraschi, Shi-Qiong Xu, Antonino Belfiore, Liliana Schaefer, Renato V. Iozzo,* and Andrea Morrione. Decorin differentially modulates the activity of insulin receptor isoform A ligands. Matrix Biology. In press.
  • Roberta Malaguarnera, Antonella Sacco, Alaide Morcavallo, Sebastiano Squatrito, Antimo Migliaccio, Andrea Morrione, Marcello Maggiolini, and Antonino Belfiore. Metformin inhibits Androgen-induced IGF-IR up-regulation in prostate cancer cells by disrupting membrane-initiated androgen signaling. Endocrinology. In press.

Individual Expertise profile of Andrea Morrione, PhD, Copyright © Andrea Morrione, PhD.
Last Updated by Andrea Morrione, PhD : Friday, March 1, 2013 2:46:05 PM



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