Dott. Luca Lazzari
- f403-c403 Dottore in Medicina Molecolare
- Dottorato: 24° ciclo
- Matricola: 295021
Contatti
- luca.lazzari@ircc.it
- IRCC - Institute for Cancer Research and Treatment
S.P.142, km 3.95
10060 Candiolo (TO) Italy - https://dott-mm.campusnet.unito.it/do/studenti.pl/Show?295021
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Supervisore
Paolo ComoglioTesi di dottorato
Study the role of ROR1 pseudokinase receptor in cancer
Data discussione tesi: 01/02/2013
Attività di ricerca
The focous of my thesis project is the study of ROR1 (Receptor-tyrosine-kinase-like Orphan Receptor 1) in human cancer. This transmembrane protein belong to the family of Receptor Tyrosine Kinases (RTKs). Very little is known about this receptor, indeed its ligand is unknown (ROR1 is classified as "orphan" receptor) and its mechanism of activation is unclear. Moreover, the involvement of this protein in cancer is very poorly investigated.
Our previous studies demonstrated that ROR1 is a pseudokinase (avoid of catalytical activity) that is specifically trans-phosphorylated by MET oncogene, indicating the involvement of this protein in MET-driven tumorigenesis. In fact, constitutive silencing of ROR1 in two MET-addicted cancer cell lines (that exhibit high level of ROR1 phosphorylation) impaired cellular proliferation, growth and migration in vitro and induced a dramatic inhibition of tumorigenesis in vivo.
Now, we are deeply analyzing the biochemical relationship between ROR1 and MET, in particular focousing our attention on the mechanism of transphosphorylation of ROR1 by MET and identification of downstream pathaways governing the biological responses driven by this couple of receptors.
Gentile A., D’Alessandro L., Lazzari L., Martinoglio B., Bertotti A., Mira A., Lanzetti L., Comoglio P.M. and Medico E. “Met-driven invasive growth involves transcriptional regulation of Arhgap12” Oncogene 2008, 27(42): 5590-5598
Benvenuti S., Lazzari L., Arnesano A., Li Chiavi G., Gentile A. and Comoglio P.M. “RON kinase trans-phosphorylation sustains MET oncogene addiction” Cancer Research 2011, 71(5): 1945-1955
Gentile A., Lazzari L., Benvenuti S., Trusolino L. and Comoglio P.M. “ROR1 is a pseudokinase that is crucial for MET-driven tumorigenesis” Cancer Research 2011, 71(8): 3132-3141
Gentile A., Lazzari L., D’Alessandro L., Medico E. and Comoglio P.M. “Arhgap12: a negative regulator of Hepatocyte Growth Factor-driven invasive growth identified by a novel gene trapping strategy” Beatson International cancer conference - 24 years of Ras and human cancer; June 18-21, 2006 Glasgow, Scotland (UK)
Gentile A., Lazzari L., Martinoglio B., Martelli M.L. and Medico E. “Arhgap12: a negative regulator of HGF-driven invasive growth identified by a novel gene trapping strategy” EMBO workshop - Stemness: the bright and the dark side.Normal and cancer stem cells; September 19-22, 2006 Catanzaro, Italy
Benvenuti S., LazzariL., Gentile A. and ComoglioPM. “RON trans-phosphorylation sustains addiction to the MET oncogene” 21st Meeting of the European Association for Cancer Research (EACR); June 26-29, 2010Oslo,Norway
Gentile A., Lazzari L., Benvenuti S., Trusolino L. and ComoglioPM. “ROR1 is a pseudokinase involved in Met-driven tumorigenesis” 21st Meeting of the European Association for Cancer Research (EACR); June 26-29, 2010Oslo,Norway
Lazzari L., Gentile A., Benvenuti S., Trusolino L. and Comoglio P.M. “ROR1 is a pseudo-kinase involved in MET-driven tumorigenesis” Nature CNIO Cancer Symposium - Frontiers in Tumour Progression; October 24-27, 2010 Madrid, Spain
Lazzari L., Gentile A., Benvenuti S., Trusolino L. and Comoglio P.M. “ROR1 is a pseudokinase that is crucial for MET-driven tumorigenesis” FEBS Advanced Lecture Course on Translational Cancer Research; September 27-October 4, 2011 Algarve, Portugal
EMBO Molecular Medicine Workshop - Invasive Growth: a Genetic Programme for Stem Cells and Cancer, September 10-12, 2009 Torino, Italy
Nature CNIO Cancer Symposium - Frontiers in Tumour Progression, October 24-27, 2010 Madrid, Spain
2011 IRCC International Conference - Molecular Clinical Oncology, May 26-28, 2011 Torino, Italy
FEBS Advanced Lecture Course on Translational Cancer Research, September 27-October 4, 2011 Hotel Porto Bay Falésia, Olhos D’agua, Algarve, Portugal
53rd SIC Annual Meeting – Back to the Future: Translating Cancer Research from Bedside to Bench and Back, October 19-22, 2011 Torino, Italy
PerkinElmer Days at Molecular Biotechnology Center - Receptor Binding & Signal Transduction, Giugno 15, 2010 Torino, Italy
FEBS Advanced Lecture Course on Translational Cancer Research, September 27-October 4, 2011 Hotel Porto Bay Falésia, Olhos D’agua, Algarve, Portugal