Professor Sara Cabodi
Contacts
E-mail: sara.cabodi@unito.it
Office: 0116706422 Fax: 0116706432
Affilition: Department of Molecular Biotechnology and Health Sciences
Sara Cabodi’s research activity has been focused in the last ten years on the study of the role of p130Cas adaptor protein in epithelial cell homeostasis and in breast cancer.
p130Cas is a signalling molecule involved in the linkage of actin cytoskeleton to the extracellular matrix during cell migration, cell invasion and cell transformation. p130Cas protein has been described as a major player in the cross-talk between EGF Receptor and integrins. Due to its modular structure, p130Cas has been described to play a crucial role in signalling originating from many amplified or mutated oncogenes, by undergoing hyperphosphorylation and association with multiple signalling partners required for transformation.
Our research has demonstrated that the over-expression of p130Cas in the mammary gland epithelium induces hyperplasia during the development and delayed involution of mouse mammary glands, due to alterations of the luminal progenitor cell fate. In addition, in vivo and in vitro studies have demonstrated a strict correlation of p130Cas expression and ErbB2 positive breast cancer. Indeed, high levels of expression of p130Cas in human ErbB2 positive breast cancer correlates with low prognosis and increased risk to develop metastasis. At the molecular level, p130Cas synergizes with ErbB2, by leading to the formation of a macromolecular signaling platform leading to activation of proliferation, migration and invasion.
The current research is focused on understanding the critical mediators of p130Cas-mediated invasion of ErbB2 transformed cells by using a 3D cell model. In addition, we are interested in understanding whether modulation of p130Cas expression can affect the homeostasis of other specialized epithelia and to address this question we have recently developed an in vivo model of skin in which p130Cas is ablated.
1: Pincini A, Tornillo G, Orso F, Sciortino M, Bisaro B, Camacho-Leal MD, Lembo A, Brizzi MF, Turco E, De Pittà C, Provero P, Medico E, Defilippi P, Taverna D, Cabodi S. Identification of p130Cas/ErbB2-dependent invasive signatures in transformed mammary epithelial cells. Cell Cycle. 2013 Jun 28;12(15).
2: Tornillo G, Elia AR, Castellano I, Spadaro M, Bernabei P, Bisaro B, Camacho-Leal Mdel P, Pincini A, Provero P, Sapino A, Turco E, Defilippi P, Cabodi S. p130Cas alters the differentiation potential of mammary luminal progenitors by deregulating c-Kit activity. Stem Cells. 2013 Jul;31(7):1422-33.
3: Camacho Leal M del P, Pincini A, Tornillo G, Fiorito E, Bisaro B, Di Luca E, Turco E, Defilippi P,Cabodi S. p130Cas Over-Expression Impairs Mammary Branching Morphogenesis in Response to Estrogen and EGF. PLoS One. 2012;7(12).
4: Cabodi S, del Pilar Camacho-Leal M, Di Stefano P, Defilippi P. Integrin signalling adaptors: not only figurants in the cancer story. Nat Rev Cancer. 2010 Dec;10(12):858-70.
5: Tornillo G, Bisaro B, Camacho-Leal Mdel P, Galiè M, Provero P, Di Stefano P, Turco E, Defilippi P, Cabodi S. p130Cas promotes invasiveness of three-dimensional ErbB2-transformed mammary acinar structures by enhanced activation of mTOR/p70S6K and Rac1. Eur J Cell Biol. 2011 Feb-Mar;90(2-3):237-48.
6: Cabodi S, Di Stefano P, Leal Mdel P, Tinnirello A, Bisaro B, Morello V, Damiano L, Aramu S, Repetto D, Tornillo G, Defilippi P. Integrins and signal transduction. Adv Exp Med Biol. 2010;674:43-54.
7: Cabodi S, Tinnirello A, Bisaro B, Tornillo G, del Pilar Camacho-Leal M, Forni G, Cojoca R, Iezzi M, Amici A, Montani M, Eva A, Di Stefano P, Muthuswamy SK, Tarone G, Turco E, Defilippi P. p130Cas is an essential transducer element in ErbB2 transformation. FASEB J. 2010 Oct;24(10):3796-808.