Dottorato in Medicina Molecolare

- Avalle L , Pensa S, Regis G, Novelli F, Poli V. Stat1 and Stat3 in tumorigenesis: a matter of balance. JAK/STAT, Landes Bioscience, 2012;1:65-72.

- Avalle L, Regis G, Poli V. Universal and specific functions of STAT3 in solid tumours. Jak-Stat Signaling: From Basics to Disease, Springer, in press 

- Pensa S, Demaria M, Avalle L, Barbieri I, Camporeale A, Poli V. From tissue invasion to glucose metabolism: the many aspects of Signal Transducer and Activator of Transcription 3 pro-oncogenic activities. HMBCI, DeGruyter, in press

- Schiavone, D., Avalle, L., Dewilde, S., & Poli, V. (2011). The immediate early genes Fos and Egr1 become STAT1 transcriptional targets in the absence of STAT3. FEBS letters, 585(15), 2455–2460. doi:10.1016/j.febslet.2011.06.020

 

2011 (FEBS and phD meetings)

STAT3 enhances migration and invasion in mammary tumor cells: a potential role for microRNAs -143 and -145.

Lidia Avalle, Isaia Barbieri, Sara Pensa, Paolo Provero, Valeria Poli

MolecularBiotechnologyCenter, Department of Genetics, Biology and Biochemistry,UniversityofTurin,Turin,Italy.

 

The transcription factor STAT3 is constitutively activated in nearly 70% of tumors, where it is known to contribute to survival, proliferation, tissue invasion and immune evasion. We have recently generated knock-in mice expressing STAT3C, a constitutively active form of STAT3, and shown that it can cooperate with the oncogene HER2 in mammary tumorigenesis (Barbieri et al., Cancer Res., 2010, 70:2558). The development of more aggressive tumors in Stat3C/MMTV-NeuT mice correlates with an increased migratory and invasive ability of tumor-derived cells, which display disrupted distribution of cell junction markers and increased in vivo metastatic potential. We found some genes upregulated in STAT3C expressing cells: Twist1, a weel-known STAT3 transcriptional target, Lgals3, Lypd3 and Cten. All these genes have been shown to play a role in regulating cell migration and/or tumor metastasis. In particular we could show that Cten, known to be required for EGF-induced cell migration, is a novel Stat3 target that plays an important role in mediating the aggressive phenotype of Stat3C cells.

We found that all STAT3C cell lines express high levels of microRNAs -143 and -145, which are known to be required for the reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce the differentiation of multipotent neural crest stem cells into vascular smooth muscle, a process involving an epithelial to mesenchymal transition (EMT). Interestingly, STAT3C cell line  that expresses the highest amounts of the microRNAs regularly generates a subpopulation of spindle-shaped cells displaying a mesenchymal-like phenotype, expressing high levels of EMT markers, and further up-regulating microRNAs -143 and -145. The potential contribution of these two miRNAs and of Twist1, Lgals3 and Lypd3 to the highly migratory and invasive phenotype of the Stat3C cells, as well as their ability to undergo an EMT-like transition is being explored.

 

2010 (GET CONNECTED and Metafight meetings)

STAT3 enhances migration and invasion in mammary tumor cells: a potential role for microRNAs-143 and -145

Lidia Avalle, Isaia Barbieri, Sara Pensa, Paolo Provero, Valeria Poli

Molecular Biotechnology Center, Department of genetics, Biology and Biochemistry, University of Turin, Turin, Italy.

The transcription factor STAT3 is constitutively activated in many tumors, where it contributes
to several processes such as proliferation and tissue invasion. We have generated knock-
in mice expressing STAT3C, a constitutively active form of STAT3, and shown that it can
cooperate with HER2 in mammary tumorigenesis (Barbieri et al., 2010). The development
of more aggressive tumors in Stat3C/MMTV-NeuT mice correlates with an increased
migratory and invasive ability of tumor-derived cells, which display disrupted distribution
of cell junction markers. We showed that Cten, known to be required for EGF-induced cell
migration, is a novel Stat3 target that contributes to the aggressive phenotype of Stat3C
cells.

We found that all STAT3C cell lines express high levels of microRNAs-143 and -145, which
are known to be required for the reprogramming of adult fibroblasts into smooth muscle cells
and other processes involving an epithelial to mesenchymal transition (EMT). Interestingly,
one STAT3C cell line generates a subpopulation of spindle-shaped cells displaying a
mesenchymal-like phenotype, express high levels of EMT markers, and further up-regulate
microRNAs-143 and -145. The potential contribution of these two miRNAs to the highly
migratory and invasive phenotype of the Stat3C cells, as well as to their ability to undergo
this EMT-like transition, is being explored.

 

- GET CONNECTED! - Wellcome Trust Centre for Cell-Matrix Research meeting 2010. Manchester, 13-15 september 2010. Poster presentation.

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

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

- ABCD Congress 2011 - Ravenna, 8-10 September 2011.

Oral presentation: "STAT3 enhances migration and invasion in mammary tumor cells: a potential role for microRNAs-143 and -145". 

Winner of ABCD Grant for Young Investigator

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

- IABCR/Breakthrough Breast Cancer Conference - Manchester, UK, 15-18 April 2012

 

2012

- GIACCA, How can you mend a broken heart: searching for genes that induce myocardial repair by in vivo gene transfer using AAV vectors (Ospite Tarone)

- DI FIORE, Endocytosis, stem cells and cancer (Ospite Tarone)

- PELICCI, Regulation of self-renewal in cancer stem cells (Ospite Tarella)

- SHEVACH, Foxp3+ T regulatory cells: what do they really do? (Ospite Forni)

- CONDORELLI, Epigenetic control of myocardial function (Ospite Deaglio/Matullo)

- KASS, Novel therapies to reverse-remodel the failing heart (Ospite Hirsch)

- DIVIANI, The multiple roles of AKAP-Lbc in cardiac remodeling (Ospite Tarone)

- RIVELLA, Fondamentale ruolo dei macrofagi in stess eritropoiesi e nello sviluppo pato-fisiologico della Beta-talassemia e policitemia vera (Ospite Tolosano)

- GARATTINI, Retinoic acid and derivatives in oncology: a rational approach (Ospite Defilippi)

- DE FRANCESCHI, Erythrocyte membrane changes of chorea-acanthocytosis are the result of altered Lyn kinase acrivity (Ospite Defilippi)

 

 2011

- 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)

- PFEIFER, The cGMP/protein kinase G in fat tissue (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)

 

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)