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Dott.ssa Federica Fusella

  • Dottorato: 25° ciclo
  • Matricola: 333455

Attività di ricerca

 

- Ferretti R., Sbroggiò M., Di Savino A., Fusella F., Bertero A., Michowski W., Tarone G., Brancaccio M. Morgana and melusin: two fairies chaperoning signal transduction. Cell Cycle, 2011 Nov 1;10(21):3678-83.

- Sbroggiò M, Bertero A, Velasco S, Fusella F, De Blasio E, Bahou WF, Silengo L, Turco E, Brancaccio M, Tarone G. ERK1/2 activation in heart is controlled by melusin, focal adhesion kinase and the scaffold protein IQGAP1. J Cell Sci. 2011 Oct 15;124(Pt 20):3515-24

- Michowski W, Ferretti R, Wisniewska MB, Ambrozkiewicz M, Beresewicz M, Fusella F, Skibinska-Kijek A, Zablocka B, Brancaccio M, Tarone G, Kuznicki J. Morgana/CHP-1 is a novel chaperone able to protect cells from stress. Biochim Biophys Acta. 2010 Sep;1803(9):1043-9.

 

2011 (FEBS meeting Turin)- 2011 (Lausanne)

MORGANA OVEREXPRESSION CONFERS RESISTANCE FROM APOPTOTIC CELL DEATH

 Fusella Federica, Ferretti Roberta, Di Savino Augusta, Tornillo Giusy, Cabodi Sara, Pier Paolo Pandolfi, Guido Tarone, Mara Brancaccio

 

Morgana has been recently reported as a protein involved in centrosome duplication and genomic stability. In mammalian cells it forms a complex with Hsp90, ROCK I and II and directly binds ROCK II inhibiting its kinase activity (Ferretti et al., 2010). Furthermore it has been described as a stress responsive protein with an intrinsic chaperone activity. It behaves like a Hsp90 co-chaperone (Michowski W. et al., 2010). Human tumor tissue arrays reveal that Morgana expression is reduced in a large fraction of samples, but interestingly the protein is strongly up-regulated in a subset of them. Here we show that NIH3T3 overexpressing Morgana are transformed in vitro and in vivo. Furthermore NIH overexpressing Morgana are more resistant to different apoptotic stimuli (detachment, serum starvation, DNA damage induced by etoposide). Our results suggest that Morgana acts as an anti-apoptotic factor by inhibiting ROCK kinase activity. In fact cells overexpressing Morgana show a reduction in MLC-2 phosphorylation. In addition with constitutively active ROCK Morgana overexpressing cells loose their ability to grow in soft agar and show a restoration of apoptosis sensitivity. Moreover, by the analysis of Morgana levels in several tumor cell lines, we also found the up-regulation of the protein in cancer cell lines. To assess the role of Morgana overexpression in breast carcinoma, expression of endogenous Morgana is knocked down in breast cancer cell. Silenced cells show reduced ability to grow in soft agar and higher rate of apoptosis upon etoposide treatment. Therefore Morgana downregulation has no effect on in vitro cell proliferation but results in reduction of anoikis resistance and decrease in cell motility. Furthermore lung colonization experiments reveale that Morgana is required for metastatic ability of cancer cells. Taken together these results provide novel insights on the role of Morgana overexpression in conferring cells some oncogenic hallmarks.

2011 (Gubbio)- 2012 (Firenze)

Morgana: a novel player in apoptotic resistance and metastatic progression in breast cancer cells

F. Fusella, R. Ferretti, A. Di Savino, G. Tornillo, S. Cabodi, A. Sapino, G. Tarone, M. Brancaccio
Molecular Biotechnology Center, Dept Genetics, Biology and Biochemistry, Univ. of Turin

Morgana has been recently reported as a protein involved in centrosome duplication and genomic stability. In mammalian cells it forms a complex with Hsp90, Rhokinase I and II. Furthermore it has been described as a stress responsive protein with an intrinsic chaperone activity. Here we show that NIH3T3 overexpressing Morgana are transformed in vitro and in vivo. Furthermore NIH overexpressing Morgana are more resistant to several apoptotic stimuli (detachment, serum starvation, DNA damage induced by etoposide). Our results indicate that Morgana acts as an anti-apoptotic factor by inhibiting ROCK I kinase activity. Indeed rescue experiments demonstrate that demonstrate Morgana overexpressing cells with constitutively active ROCK show a restoration of apoptosis sensitivity.
Moreover, by the analysis of Morgana expression in several tumor cell lines, we also found the up-regulation of the protein in aggressive cancer cell lines.
To assess the role of Morgana overexpression in breast carcinoma, expression of endogenous Morgana is knocked down in breast cancer cells. Silenced cells show reduced ability to grow in soft agar and a higher rate of apoptosis upon etoposide treatment. Therefore Morgana downregulation has no effect on in vitro cell proliferation but results in reduction of anoikis resistance and decrease in cell motility. Besides, lung colonization experiments reveal that Morgana is required for metastatic ability of cancer cells. In addition human breast tumor tissue histochemical arrays suggest a strong correlation between Morgana expression and the degree of tumor malignancy.
Taken together these results provide novel insights on the role of Morgana overexpression in conferring cells some oncogenic hallmarks.

 

- MetaFight Workshop - Unravelling Cancer Cell Invasion and Metastasis. Turin, 2-3 december 2010.

- 36th FEBS Congress - Biochemistry for tomorrow's Medicine. Turin, 25-30 June 2011. Poster presentation

- Hallmarks and horizons of cancer. Lausanne, 7-10 Semptember 2011. Poster presentation

- Joint National PhD meeting. Gubbio, 20-22 October 2011. Poster presentation

- ABCD Mechanisms of Signal Transduction. Firenze, 16-17 March 2012. Oral presentation

- 28th IABCR/Breakthrough Breast Cancer Conference. 15-18 April 2012.

 

2012

- GIACCA, How con you mend a broken heart: searching for genes that induce myocardical repair by in vivo gene transfer using AAV vector (ospite Tarone)

- DI FIORE, Endocytosis. Stem cells and cancer (ospite Tarone)

- PELLICCI, Regulation of self-renewal in cancer stem cells (ospite Tarella)

2011

- BRISKEN, Genetic dissection of hormonal control mechanisms in breast development and carcinogenesis, (ospite  Cabodi)

- DELLA FAVERA, The genome of B cell lymphoma, (ospite Tarella)

- ALBIGES-RIZO, Dynamics of focal adhesion and angiogenesis, (ospite De Filippi)

- SCHMITT, The senescence-host immune connection in cancer, (Ospite Pandolfi)

- ALIMONTI, Manipulation of senescence pathways for cancer therapy from experimental model to clinic (Ospite Pandolfi)

- KAIRBAAN HODIVALA DILKE, Dose matters and angiogenesis (Ospite Taverna)

- THOMAS THUM, Cardiovascular microRNAs: mechanism, therapeutic strategies and biomarker approaches

- PASCAL MEIER, Ubiquitin-mediated regulation of cell survival (Ospite Santoro)

- JUDITH VARNER, PI3Kgamma and tumor inflammation (Ospite Hirsch)

- BIRCHMEIER, Wnt beta- catenin and Met signalling in stem and cancer stem cells (Ospite Tarone)

- PEEPER, Senescence and cancer, (ospite Pandolfi)

- SCOTT, Kinase anchoring and cancer signaling, (ospite Hirsch)

- PANDOLFI, The ceRNA hypothesis and the non-coding evolution in cancer research and therapy (Ospite Matullo)

- PFEIFER, Role of cGMP/protein kinase G in fat tissue (Ospite Hirsch)

- CHIARLE, Eventi molecolari che precedono e seguono una traslocazione cromosomica (Ospite Tarone)

- BARBACID, Targeting K-Ras signaling in cancer (ospite Ponzetto)

- ALT, Mechanisms of long range chromosomal rearrangements and translocationsin the immune system (ospite Chiarle)

- BERNARDI, The role of hypoxis response in leukemogenesis: a view from acute promyelocytic leukemia (ospite Tarone)

 

2010

- STREULI, The essential role of Integrins in controlling development and epithelial funcion in mammary gland (ospite Defilippi)

- PANDOLFI, New advances on NPM and its mutated NPMc+ version in tumorigenesis (ospite Tarone)

- PANDOLFI, A new microRNA proto-oncogenic network that downregulates PTEN in cancer (ospite Tarone)

- OTTENSMEIERIC, DNA vaccines against cancer: the Southampton perspective (ospite Forni)

- BAZZONI, A regulatory circuitry involving miR-9 and Nf-Kb controls neutrophils and monocytes activation by LPS (ospite Poli)

-SCHMID, Tumor inflammation and progression depend on PI3Kgamma mediated activation of Integrin beta1 (ospite Hirsch)

- MERICSKAY, SRF: a master regulator of cytoskeletal genes (ospite Tarone)

- HYNES, Targeting receptor tyrosine kinases in breast cancer (ospite Taverna)

- GINESTIER, Breast cancer stem cells (ospite Cabodi)

- TORTI, Recent advancements in platelet Integrin signaling: the role of PI3K-beta and PYK2 (ospite Hirsch)

 

- “Cellular senescence, in aging, stem cell biology, tumor suppression and therapy”, tenuto dal Prof. Pandolfi, della durata di 4 giorni (14-15, 18-19 Aprile 2011)

- "Stem cells", tenuto dal Prof. Pandolfi, della durata di 3 giorni (15-16-17 maggio 2012)

 

 



 

Ultimo aggiornamento: 15/02/2013 15:21
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