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Molecular and functional characterisation of signalling platforms and translational strategies

Prof.ssa Paola Defilippi (Principal Investigator)

 

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Activities

The scientific activity had focused on integrin signaling withspecial interest for the study of the pathophysiology of integrin-and growth factor- dependent interactions in mesenchymal and epithelia cells. We use cellular and molecular biology techniques over the years, generating new cell and animal models to investigate deeply signaling pathways and their functional relevance. This lab was one of the first to provide evidence of an extensive cross-talk between beta1 integrin and EGF receptor (EGFR) that involves physical interaction among the proteins at the cell surface (EMBO J. 1998 PMID:9822606; JBC 2002 PMID:11756413). By mass spectrometry analysis we also showed differential phosphorylation of EGFR tyrosines upon integrin or EGF-dependent activation (Mol Cell Prot 2005, PMID:15901825). This work also established that Integrin/EGFR cross talk is essential for priming EGFR activity in normal and cancer cells (Oncogene 2011 PMID:21478906).

This group had identified and fully characterized at the genetic and functional level adaptor proteins that build up very upstream molecular platforms in integrin/RTK-dependent signals. Among them, the p130Cas and p140Cap adaptor proteins have been extensively studied in cell and animal models, providing evidence of their role in the control of pathways leading to cytoskeleton organization, cell motility and cell invasion (Cancer Res 2006 PMID:16651418; EMBO J 2007 PMID:17525734; Oncogene 2010 PMID:20453886; Oncogene 2012 PMID:21725361; Cell Commun Signal. 2018 PMID:30477510). This is particularly relevant in cancer cells, regulating cancer progression (Nat Rev Cancer 2010, PMID:21102636; Breast Can Res 2014 PMID:25606587; Nat Commun 2017 PMID 28300085; Sci Signal 2017 28377405; Sci Rep. 2019 PMID:30816273, Cell Death and Diff 2019 PMID:31488891).

Recently my group had established that the p140Cap adaptor is highly expressed in neurons, with an enrichment in synaptic structures, where it participates in dendritic spine remodeling (Neuron 2009 PMID:19146815; Nat Comm 2013 PMID:23868368; J Neurosc 2014 PMID:24453341), in synaptogenesis and development of hippocampal inhibitory circuits (PNAS 2016 PMID 27506785; Front Mol Neurosc 2017 PMID 28713243; Cer Cortex 2017 PMID:29161354) and in drug addiction (PNAS, 2016, PMID:27506785; J of Neuros 2019 PMID:31092585)

Recently we extensively employed proteomics, to converge on p140Cap interactors by mass spectrometry in synaptosomes and breast cancer Front Mol Neurosci, 2017, PMID:28713243; Front Cell Dev Biol. 2019 PMID:31681758. We show that the functional signature of the two interactomes is primarily determined by organ/tissue and functional specificity, with on overlap of shared functional terms, which might be linked to both cancer and neurological functions. We are investigating the relevance of the interacting pathways in functional events, as well as in diagnosis and therapies.

 

Group

Prof.ssa Paola Defilippi

  • AIRC (Associazione Italiana Ricerca Cancro) 2018 – 2022
  • DEFLECT Digital tEchnology For Lung Cancer Treatment 2018-2020
  • Contributo CRT
  • Ricerca locale 2019 
 

 

Ultimo aggiornamento: 08/04/2022 12:07