Activation dymanics and cooperativity between erbB receptors family and focal adhesion proteins in breast cancer cells.

TOSACNI ANDRES MARTIN; COLUCCIO LESKOW F

Bariloche

Congreso; SISTAM 2012; 2012

Activation dynamics and cooperativity between erbB receptors family and focal adhesion proteins in breast cancer cells Toscani, AM1, Coluccio Leskow, F1 1-Department of Biological Chemistry, IQUIBICEN-CONICET, School of Exact and Natural Sciences, UBA, Buenos Aires, Argentina. The Epidermal Growth Factor Receptor (EGFR) family are type I transmembrana proteins that participate in growth and differentiation of several tissues. The EGFR family is form by four members: EGFR, erbB2, 3 and 4. While the EGF can activate both EGFR and erbB4, erbB3 has higher affinity for heregulin-1 (HRG-1). ErbB2 forms clusters in the membrane while is not activated. After EGF or HRG-1 stimulation, erbB2 forms heterodimers with EGF or erbB3, respectively. EGFR family proteins are overexpressed in several tumors like prostate, bone, lung and breast, among others. Particularly, erbB2 is a bad prognosis marker. It has been reported that erbB2 can interact with focal adhesion proteins, like 1-Integrin or Focal Adhesion Kinase (FAK), although the relevance of such interaction in both normal and tumoral tissues has not yet been cleared. The aim of the present work is to characterize the interaction between erbB family receptors, particularly erbB2 and 3, with focal adhesion proteins and its relevance in tumor cell physiology. Preliminary results show that erbB2 colocalization with 1-integrin in breast bancer cell line MCF7 highly depends on the extracellular cell matrix. While there is a positive colocalization between these proteins in uncoated or Laminin-coated coverslips, Fibronectin disrupts such interaction. Also, we found that activation of adhesion molecules by both soluble and surface-coated Fibronectin alters the phosphorilation dynamics of AKT by activation of erbB2/3 heterodimer with HRG-1. With this work we aim to shed light into the complex activation patterns of EGFR family receptors that will help in the development of new therapeutical approaches to treat cancer.